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KembaraXtra-Medicine – Amyotrophic Lateral Sclerosis (ALS)
Amyotrophic lateral sclerosis (ALS) is a progressive and fatal degenerative neuromuscular condition of undetermined etiology that affects the corticospinal tracts and anterior horn cells, resulting in dysfunction of both upper motor neurons (UMNs) and lower motor neurons (LMNs). Synonyms include Lou Gehrig disease, ALS, and motor neuron disease. The ICD-10CM code is G12.21 (Amyotrophic lateral sclerosis).
ALS incidence is about two new cases per 100,000 persons per year. Onset is usually between 50 and 70 years, and the male-to-female ratio is 1.8:1. The estimated prevalence is 5.2 per 100,000 population.
Clinical presentation typically includes a combination of LMN signs—weakness, hypotonia, muscle wasting, fasciculations, and hyporeflexia or areflexia—and UMN signs—loss of fine motor dexterity, spasticity, extensor plantar responses, hyperreflexia, and clonus. Extraocular movements, sensation, and bowel and bladder function are typically preserved. Patients may develop dysarthria, dysphagia, pseudobulbar affect, and frontal lobe dysfunction. Respiratory insufficiency progresses to respiratory failure and death, typically late in the disease. Concomitant frontotemporal dementia occurs in about 15%, and executive dysfunction occurs in another 50%. Pseudobulbar affect (inappropriate crying or laughing not triggered by typical emotional cues) is common and treatable.
ALS commonly manifests in one of three onset patterns. Limb onset accounts for 75%–80% of cases and presents with painless muscle weakness, clumsiness (dropping things, stumbling, falling), impaired fine motor skills (e.g., writing), limb stiffness, gait disturbances, and wristdrop or footdrop. Bulbar onset accounts for 20%–25% and presents with dysarthria or voice change, pseudobulbar affect, dysphagia and/or weight loss, drooling, and choking during swallowing. Respiratory onset occurs in <3% and presents with dyspnea on exertion or at rest, orthopnea, daytime sleepiness, difficulty sleeping, other symptoms of respiratory compromise. als makes up about 90% adult-onset motor neuron diseases; disease presentations include progressive muscular atrophy, primary lateral sclerosis, bulbar palsy, pseudobulbar als-parkinsonism-dementia complex.< />pan>
Regarding etiology and classification, 90% of cases are sporadic and 10% are familial. Known genetic mutations include C9orf72 hexanucleotide repeat expansion (responsible for ~40% of familial ALS among those of European origin and nearly 10% of sporadic ALS, and virtually all ALS cases associated with frontotemporal dementia), SOD1 (copper-zinc superoxide dismutase) mutations (~12% of familial cases), TAR DNA-binding protein mutations (~4% of familial cases), and FUS (~4% of familial cases, rarely associated with frontotemporal dementia), among many others. Risk is increased in Whites, non-Hispanics, age >60 years, family history of ALS, and prior exposure to heavy metals, pesticides, or BMAA. A practical classification includes sporadic/acquired ALS variants (classic spinal-onset, Mills hemiplegic variant, pseudoneuritic, flail-arm, monomelic, UMN onset, LMN onset, bulbar onset, dyspnea onset, progressive muscular atrophy, primary lateral sclerosis, progressive bulbar palsy, Western Pacific ALS) and multiple familial ALS subtypes (ALS1 through ALS25 and additional rare-mutation forms). An FTD-ALS overlap is also recognized (e.g., ALS-FTD associated with C9orf72; and FTD with some ALS features associated with tau and progranulin genes on chromosome 17).
The differential diagnosis includes multifocal motor neuropathy with conduction block; cervical spondylotic myelopathy with polyradiculopathy; spinal stenosis with lumbosacral nerve root compression; chronic inflammatory demyelinating polyneuropathy with CNS lesions; syringomyelia; syringobulbia; foramen magnum tumor; meningeal carcinomatosis; spinal muscular atrophy; polyglucosan body disease; bulbospinal muscular atrophy (Kennedy disease); monomelic amyotrophy; Lyme disease; and ALS-like syndromes reported with lead intoxication, HIV, hyperparathyroidism, hyperthyroidism, lymphoma, and vitamin B12 deficiency.
Diagnosis is based on clinical findings, electromyography results, and exclusion of alternative causes. Workup includes MRI of brain and spine to exclude mimics; electromyography and nerve conduction studies following Revised El Escorial criteria; assessment of respiratory function (forced vital capacity [FVC], negative inspiratory force); assessment of swallowing and nutritional status; and neuropsychologic testing if executive dysfunction or FTD is a concern. The Revised El Escorial criteria require evidence of LMN degeneration (clinical, electrophysiologic, or neuropathologic), evidence of UMN degeneration (clinical), and progressive spread of symptoms/signs within or between regions, together with absence of electrophysiologic/pathologic evidence of another disease explaining UMN/LMN degeneration and absence of neuroimaging evidence of another explanatory disease process. Levels of certainty include Definite ALS (UMN and LMN signs in three regions), Probable ALS (UMN and LMN signs in two regions with UMN signs rostral to LMN signs), Probable ALS—Laboratory Supported (UMN signs in one or more regions with LMN signs by EMG in at least two regions), and Possible ALS (UMN and LMN signs in one region together, or UMN signs in two or more regions, or UMN and LMN signs in two regions without UMN signs rostral to LMN signs).
Laboratory tests that may be considered include vitamin B12, thyroid function, parathyroid hormone, and HIV, plus serum protein electrophoresis with immunofixation. In pure LMN syndromes, consider DNA studies for spinal muscular atrophy, bulbospinal atrophy (Kennedy disease), and hexosaminidase levels (late-onset Tay-Sachs). A 24-hour urine heavy metal screen may be done if indicated. In familial ALS, genetic studies should be performed with appropriate genetic counseling. Imaging is guided by clinical scenario; MRI brain and spinal cord help exclude structural mimics, and a modified barium swallow evaluates aspiration risk.
Treatment includes symptomatic management plus disease-modifying therapy that slows progression in some patients. Symptomatic treatment options span multiple domains: fatigue (pyridostigmine bromide, antidepressants, methylphenidate, amantadine, modafinil; energy conservation, work modification, sleep study with BiPAP if abnormal), spasticity (baclofen, tizanidine, dantrolene sodium, diazepam; physical therapy, range-of-motion exercises, botulinum toxin), jaw clenching (benzodiazepines, botulinum toxin into masseters), cramps (quinine sulfate, baclofen, vitamin E, clonazepam; massage, physical therapy), fasciculations (carbamazepine and reassurance), sialorrhea (hyoscyamine sulfate, diphenhydramine, scopolamine patch, glycopyrrolate, atropine, TCAs; suction machine, botulinum toxin into salivary glands, parotid radiation therapy, steam inhalation, nebulization, dark grape juice), pseudobulbar laughing/crying (TCAs, SSRIs, L-dopa/carbidopa, lithium, mirtazapine, venlafaxine, quinidine/dextromethorphan), thick phlegm (guaifenesin, nebulized N-acetylcysteine, nebulized saline, propranolol; insufflation-exsufflation, high-flow chest wall oscillation therapy, cool mist humidifier, rehydration, pineapple/papaya juice, reduced dairy/caffeine/alcohol), aspiration (cisapride and modified food consistency; in severe cases tracheostomy or modified laryngectomy with tracheal diversion), joint pains (anti-inflammatory drugs, analgesics, range-of-motion and heat), depression (TCAs; SSRIs/venlafaxine/mirtazapine/bupropion; counseling, support groups, psychiatry), insomnia (zolpidem tartrate, lorazepam, opioids, TCAs; pressure air pad/gel mattress; noninvasive ventilation where appropriate), laryngospasm (sublingual lorazepam), respiratory failure (bronchodilators, morphine sulfate; hospital bed, nocturnal noninvasive ventilator, IPPB), and constipation (increase oral fluids, Metamucil, Dulcolax suppositories, lactulose/other laxatives, exercise, “power pudding” of prune juice/prunes/applesauce/bran).
Nonpharmacologic therapy is central. Noninvasive ventilation can improve quality of life and may increase tracheostomy-free survival in patients with respiratory difficulty (orthopnea or FVC ≤50% predicted). Percutaneous endoscopic gastrostomy (PEG) can improve nutrition, stabilize weight, and ease medication administration; some studies suggest it may prolong life by 1–4 months, especially when placed before FVC falls to ≤50% predicted. Supportive services include nutrition support, speech therapy, physical and occupational therapy, suction devices for sialorrhea, cough assist devices for ineffective cough and airway clearance, and computerized assistive communication devices. Early advance-care planning discussions should address living will, resuscitation orders, preferences regarding PEG and tracheostomy, and long-term care options, and patients should be encouraged to connect with local support groups.
Disease-modifying medications do not cure ALS but can slow progression in selected patients. Riluzole (glutamate antagonist) was the first FDA-approved medication shown to extend tracheostomy-free survival; typical dosing is 50 mg every 12 hours, taken at least 1 hour before or 2 hours after meals, and it prolongs survival by about 2–3 months; ALT monitoring is recommended monthly for the first 3 months, then every 3 months until completion of the first year, and periodically thereafter. Edaravone (FDA approved 2017) slowed physical decline by 33% versus placebo in a 6-month phase III trial; it is given IV with an initial cycle of daily infusions for 14 days followed by 14 days off, then subsequent cycles of 10 infusions over 14 days followed by 14 days off; cost and insurance coverage can be limiting. Relyvrio (sodium phenylbutyrate/taurursodiol) is an FDA-approved oral fixed-dose combination (approved 2022) for adults with ALS that helps slow progression; its exact mechanism is unknown, but it targets endoplasmic reticulum and mitochondria-dependent neuronal degeneration pathways, and is thought to reduce neuronal death and dysfunction.
Chronic management includes targeted symptom control such as treating sialorrhea with glycopyrrolate or amitriptyline (and considering propranolol or metoprolol if secretions are thick), using botulinum toxin if refractory; treating spasticity with baclofen, tizanidine, or clonazepam; and treating pseudobulbar affect with amitriptyline, sertraline, or dextromethorphan/quinine.
Disposition reflects the progressive nature of ALS: there is currently no cure, mean symptom duration is 3-5 years, and about 20% of patients survive more than 5 years. Referral to a neurologist experienced in neuromuscular disease is recommended to confirm diagnosis, and multidisciplinary ALS clinics may improve survival. Gastroenterology referral for PEG placement is recommended while FVC remains >50% to reduce procedural morbidity, and pulmonology referral is appropriate for noninvasive ventilation such as BiPAP.
Pearls include the importance of patient-physician communication at diagnosis and throughout care, and the value of a multidisciplinary supportive approach to improve daily functioning and independence. Related content includes patient information resources on ALS.
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KembaraXtra-Medicine – Amphetamine Use Disorder
Amphetamine use disorder is a pattern of amphetamine use marked by impairment in control of use or social obligations, risky use, or physical dependence within a 12-month period. Severity is categorized as mild, moderate, or severe based on the number of symptoms. Amphetamines are central nervous system stimulants that increase monoamine neurotransmitters (dopamine, norepinephrine, serotonin) and are defined by a phenylethylamine structure. Amphetamine and dextroamphetamine are FDA approved for AD/HD, narcolepsy, and obesity. Methamphetamine is a type of amphetamine that is FDA approved for AD/HD and obesity, but is more commonly illicitly produced and used recreationally. Synonyms include stimulant use disorder and methamphetamine use disorder. ICD-10CM codes include F15.10 (mild), F15.20 (moderate or severe), F15.11 (mild, in early or sustained remission), and F15.21 (moderate or severe, in early or sustained remission).
Epidemiologically, prevalence is described as rare: 0.6% among people ages ≥12 years (about 1.5 million) with methamphetamine use disorder, and 0.3% among people ≥12 years (about 758,000) with prescription stimulant use disorder. Among adults who used methamphetamine in the past year, 53% met criteria for methamphetamine use disorder. Methamphetamine use disorder is more common among those age 26 and older (0.6%) than under age 25, while prescription stimulant use disorder is more common between ages 12 and 25 compared with ≥26.
Risk increases in people with any substance use disorder. Among psychiatric comorbidities, bipolar disorder, schizophrenia, and antisocial personality disorder are associated with stimulant use disorder. Demographic risk factors for methamphetamine use include male sex, lower educational attainment, and non-Hispanic White ethnicity. Methamphetamine use is higher among men who have sex with men, including in “chemsex,” where methamphetamine and other stimulants are used to increase arousal and reduce inhibition during sexual sessions.
Clinically, amphetamine use disorder can develop as quickly as within 1 week of exposure, and most people experience physical dependence in the form of tolerance or withdrawal. Amphetamines may be used by oral ingestion, insufflation, injection, or smoking, and use is often described as chronic or episodic binges. During intoxication, patients may report euphoria and may present with hyperarousal, aggressive behavior, psychosis (paranoia and hallucinations), panic attacks, or suicidal and homicidal ideation. With toxicity, sympathomimetic signs such as hypertension, tachycardia, dilated pupils, and flushed skin can occur. Some intoxicated patients report chest pain, and amphetamine use increases risk of myocardial infarction, arrhythmias, and strokes. During withdrawal, patients commonly report depressive symptoms. Risk for psychosis increases with higher frequency and amount of use, and psychosis can occur within months to several years after starting amphetamine use.
The exact cause of amphetamine use disorder is not known, but amphetamine-type medications act on the dopamine and monoamine transporter (DAT and VMAT2), increasing dopamine transmission in the mesolimbic dopamine pathway (the reward pathway).
In diagnosis, amphetamine use disorder is different from amphetamine misuse, which refers to use inconsistent with prescription guidelines. Patients using PCP or novel psychoactive substances (such as cathinones/bath salts) may present similarly and can be distinguished with a toxicology test. Primary psychiatric disorders (e.g., schizophrenia) or depressive disorders (e.g., major depressive disorder) can be evaluated by establishing a timeline of symptoms relative to amphetamine use; psychosis that quickly improves is more consistent with amphetamine-induced psychosis.
Work-up may be difficult because detailed history can be hard to obtain during acute intoxication or withdrawal. An ECG should be performed in patients with tachycardia. A safety assessment is essential to determine whether the patient can safely care for themselves, especially when suicidal or homicidal ideation is reported. Recommended labs include basic testing such as Chem 7, serum lactate, creatine phosphokinase, thyroid function tests, and hepatic enzymes. A urine or serum toxicology test can confirm amphetamine presence. There are no radiographic tests for diagnosis of stimulant use disorder, but CT imaging may be considered for strokes or vasculopathies associated with amphetamine use.
Treatment is primarily nonpharmacologic, with behavioral interventions as the mainstay. Approaches such as contingency management, cognitive-behavioral therapy, behavioral activation, and exercise have shown mild effectiveness in reducing symptoms and sustaining abstinence. Contingency management, especially when combined with community reinforcement (reorganizing the environment so abstinence is more rewarding than drug use), has been particularly shown to be effective.
For acute general management, antipsychotics—especially olanzapine and haloperidol—have evidence for treating amphetamine-associated psychosis. No medication has been shown to be effective for amphetamine withdrawal. There is limited evidence that amineptine (a tricyclic antidepressant no longer available due to abuse potential) reduced discontinuation symptoms and improved clinical presentation, and there is mixed evidence that mirtazapine may reduce anxiety symptoms during withdrawal.
For chronic management, there is no evidence that pharmacologic treatment alone is sufficient. Randomized controlled trials show limited benefit from methylphenidate, bupropion, modafinil, and naltrexone in reducing amphetamine use.
Disposition-wise, methamphetamine use disorder often follows a course of intense use, sobriety, and relapse. Complications of amphetamine intoxication (including ecstasy) include hyponatremia due to SIADH (very rare; managed with water restriction), intracerebral hemorrhage (uncommon; CT/MRI if focal signs or reduced GCS), serotonin toxicity (uncommon; supportive care and cyproheptadine for serious cases), hypertension (uncommon; GTN infusion, benzodiazepines, labetalol; avoid beta-blockers), hyperthermia (common; cooling measures, diazepam, cyproheptadine), rhabdomyolysis (uncommon; IV fluids and cooling), supraventricular and ventricular tachycardia (uncommon; short-acting antiarrhythmics such as esmolol for SVT), and seizures (uncommon; IV diazepam).
Referral is typically to physicians and mental health professionals. Important pearls include that stimulant use disorders often co-occur with sedative substance use disorders (e.g., alcohol, marijuana, opioids) because these may relieve stimulant side effects such as insomnia and anxiety. Amphetamine use is also associated with an increased risk of death by suicide, so assessing suicidality is critical in any patient presenting with amphetamine use.
For prevention, community-based universal prevention programs that promote youth social-emotional skills and reduce risk factors have been shown to lead to sustained reductions in lifetime methamphetamine use.
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KembaraXtra-Medicine – Amenorrhea
Amenorrhea means the absence of menstruation. It is classified as primary or secondary depending on whether the patient has had previous menstrual cycles. A workup for primary amenorrhea is indicated for any adolescent age 15 or older who has not reached menarche, or who does not reach menarche within 3 years of thelarche. Secondary amenorrhea is defined as the absence of menses for more than 6 months in a patient who previously had normal menstrual progesterone withdrawal cycles. ICD-10CM codes include N91.0 (Primary amenorrhea), N91.1 (Secondary amenorrhea), and N91.2 (Amenorrhea, unspecified).
From an epidemiologic standpoint, the incidence in the United States is <1% for primary amenorrhea and 5% to 7% secondary amenorrhea, with no racial or ethnic predilection.< />pan>
Amenorrhea can be physiologic or pathologic. Physiologic causes include pregnancy, lactation, constitutional delay of puberty, and menopause. Pathologic causes differ by whether amenorrhea is primary or secondary. For primary amenorrhea, major categories include hypergonadotropic hypogonadism (including 45,X, 46,XX, 46,XY, and 46,XX with gonadal failure), eugonadism (including Müllerian agenesis, vaginal septum, imperforate hymen, polycystic ovarian syndrome, congenital adrenal hyperplasia, Cushing disease, thyroid disease, and androgen insensitivity), and hypogonadotropic hypogonadism (including constitutional delay, GnRH deficiency, and other CNS disease). For secondary amenorrhea, common causes include PCOS (about 28%), eating disorders/stress (about 15.5%), hypothyroidism (about 1.5%), Sheehan syndrome (about 1.5%), Cushing syndrome (about 1%), pituitary tumor/empty sella (about 2%), pituitary diseases (about 5%), eating disorders/stress (about 2%), nonclassic congenital adrenal hyperplasia (about 0.5%), ovarian tumor (about 1%), hyperprolactinemia (about 13%), and anatomic causes (about 7%, including Asherman syndrome). An abnormal karyotype is also listed as a possible contributor in secondary amenorrhea (0.5%).
Among congenital anatomic causes of primary amenorrhea with normal breast development (cervix not visible on pelvic exam; short vagina that may be absent or obstructed), key diagnoses include Müllerian agenesis, androgen insensitivity (AI), transverse vaginal septum, and imperforate hymen. These account for about 15%, 1%, 3%, and 1% of primary amenorrhea cases, respectively; among those with apparent obstruction or absence of the vagina, proportions are approximately 75%, 5%, 15%, and 5%, respectively. Chromosomes are 46,XX for Müllerian agenesis, transverse vaginal septum, and imperforate hymen, and 46,XY for androgen insensitivity. Gonads are ovaries in Müllerian agenesis, transverse vaginal septum, and imperforate hymen, and testes in androgen insensitivity. Serum testosterone is at normal female levels in Müllerian agenesis, transverse vaginal septum, and imperforate hymen, and at normal male (high) levels in androgen insensitivity. The vagina is absent or shallow in Müllerian agenesis and androgen insensitivity, obstructed by a septum (thick or thin; high or low) in transverse vaginal septum, and obstructed by a thin membrane (sometimes bluish from hematocolpos) in imperforate hymen. Axillary/pubic hair is present in Müllerian agenesis, transverse vaginal septum, and imperforate hymen, but absent in complete androgen insensitivity (unless incomplete). Cyclic pain may be variable in Müllerian agenesis, absent in androgen insensitivity, and present in transverse vaginal septum and imperforate hymen. The uterus is absent or rudimentary in Müllerian agenesis, absent in androgen insensitivity, and present in transverse vaginal septum and imperforate hymen. A mass is typically absent in Müllerian agenesis and androgen insensitivity, but may be present in transverse vaginal septum and imperforate hymen and can cause acute urinary retention due to hematocolpos obstructing the urethra; with imperforate hymen, the introitus may bulge with Valsalva. Associated anomalies include urinary tract and skeletal anomalies in Müllerian agenesis, inguinal hernias and risk of gonadal malignancy in adulthood in androgen insensitivity, major urinary tract abnormalities in ~15% with transverse vaginal septum, and possibly some increased urinary tract abnormalities in imperforate hymen. Treatment includes vaginal dilation or surgical neovagina for Müllerian agenesis and transverse vaginal septum, gonadectomy after age 16–18 for androgen insensitivity, surgery tailored to septum extent/location (often as soon as possible) for transverse vaginal septum, and excision of hymen as soon as possible for imperforate hymen (diagnostic needle aspiration is contraindicated due to infection risk). Fertility usually requires advanced reproductive technology (including IVF with a surrogate uterus) in Müllerian agenesis, is not possible in androgen insensitivity, is variable in transverse vaginal septum (low septa have better prognosis than high septa), and is usually preserved in imperforate hymen.
Clinical presentation varies by etiology. Turner syndrome usually presents with primary amenorrhea (unless mosaic) and may include short stature, epicanthic folds, low-set ears, high-arched palate, micrognathia, sensorineural hearing loss, otitis media, webbed neck, pigmented nevi, square/shield chest, widely spaced nipples, absent breast development, bicuspid aortic valve, coarctation of the aorta, cubit valgus, short fourth metacarpal, hyperconvex nails, leg edema, renal abnormalities, and autoimmune/metabolic issues including thyroiditis and diabetes mellitus. Pure gonadal dysgenesis causes amenorrhea but lacks Turner’s dysmorphic features. Müllerian agenesis is typically sporadic and presents with primary amenorrhea, normal breast development, normal pubic/axillary hair, normal female external genitalia, absent uterus and upper vagina, and present ovaries; some patients have renal and vertebral anomalies, and renal agenesis should be evaluated. Transverse vaginal septum and imperforate hymen present with primary amenorrhea, progressive cyclic lower abdominal pain, exam findings of septum/hymen abnormality, and perirectal fullness from hematocolpos. Androgen insensitivity syndrome presents with primary amenorrhea, may be X-linked recessive in some, with normal breast development, absent pubic/axillary hair, possible testes in groin/inguinal canal, and absent uterus and vagina, without renal/vertebral anomalies. Adult-onset congenital adrenal hyperplasia is more frequent in Ashkenazi Jewish, Inuit Native American, French Canadian, and Mexican populations, mimics PCOS, causes hyperandrogenism (virilization, hirsutism, acne), and can be associated with hypertension. 5-alpha reductase deficiency may cause primary amenorrhea with virilization at puberty. PCOS often presents with secondary amenorrhea/oligomenorrhea and is diagnosed by at least 2 of 3 Rotterdam criteria (oligo/anovulation, hyperandrogenism, polycystic ovaries on ultrasound defined by ≥12 follicles 2-9 mm or ovarian volume >10 cm³); it is associated with metabolic syndrome/obesity (60%–80%), insulin resistance, and predisposition to type 2 diabetes. Cushing syndrome (rare; prevalence about 1/1,000,000) can cause secondary amenorrhea, hyperandrogenism, dorsocervical fat pad, central obesity with thin extremities, abdominal striae, easy bruising, hypertension, and proximal muscle weakness. Hypothyroidism can cause secondary amenorrhea with lethargy, constipation, decreased appetite, weight gain, cold intolerance, hair loss, dry skin, and bradycardia. Primary ovarian insufficiency (previously premature ovarian failure) presents with secondary amenorrhea before age 40 with elevated FSH/LH, possible history of oophorectomy/radiation/chemotherapy, vasomotor symptoms, and thin dry vaginal mucosa without rugosity, and may be associated with autoimmune/karyotypic abnormalities. Hyperprolactinemia commonly causes secondary amenorrhea and may be medication-related (antipsychotics, OCPs, antidepressants, antihypertensives, H2 blockers, opioids, etc.) or due to pituitary adenoma (headache, vomiting, vision changes), and may present with galactorrhea. Sheehan syndrome follows postpartum hemorrhage with secondary amenorrhea, failure of lactation, and other hypopituitarism features. Asherman syndrome is associated with a history of D&C, secondary amenorrhea, and recurrent miscarriage/infertility. Functional hypothalamic disorders cause secondary amenorrhea associated with eating disorders, excessive exercise, stress, or street drug use. Kallmann syndrome is associated with anosmia due to developmental defects of GnRH neurons and the olfactory placode.
Diagnosis begins with the first step: rule out pregnancy using a serum or urine pregnancy test. Further evaluation depends on history and physical exam, including assessment of breast Tanner stage and whether a uterus is present, since the combination of present breasts with absent uterus narrows the differential primarily to Müllerian agenesis or androgen insensitivity syndrome. In primary amenorrhea, pelvic ultrasound or MRI is used to detect anatomic abnormalities of the uterus, cervix, ovaries, or vagina. Karyotyping is performed when the uterus is absent or Turner syndrome is suspected (e.g., 46,XX in Müllerian agenesis, 46,XY in AIS, 45,XO in Turner syndrome). Recommended labs include FSH, TSH/FT4, prolactin, and estradiol; an FSH ~40 mIU/mL with estradiol <20 pg />L suggests primary ovarian insufficiency, and prolactin >200 ng/mL suggests prolactinoma (noting thresholds vary by lab). Serum testosterone is checked when the uterus is absent or hyperandrogenism is present (male-range in AIS; female-range in Müllerian agenesis). 17-alpha hydroxyprogesterone is checked when hyperandrogenism is present to rule out CAH; these patients may also have elevated progesterone and deoxycorticosterone, hypernatremia, and hypokalemia. MRI of the head is obtained in the presence of hyperprolactinemia, visual field defects, or signs of hypothalamic–pituitary dysfunction.
In secondary amenorrhea, evaluation includes FSH, TSH/FT4, prolactin, and estradiol; low FSH with low estradiol indicates hypogonadotropic hypogonadism, and high FSH with low estradiol indicates hypergonadotropic hypogonadism. A progesterone withdrawal test is performed by giving medroxyprogesterone 10 mg for 10 days; withdrawal bleeding suggests euestrogenic anovulation with normal outflow tract and ovarian function. If no bleeding occurs, an estrogen-progesterone withdrawal is done using 25-35 days of estrogen (Premarin 0.625-2.5 mg daily) followed by 10 days of medroxyprogesterone; withdrawal bleeding indicates hypogonadism, while lack of bleeding suggests an end-organ/outflow tract problem such as Asherman syndrome. When hyperandrogenism is present, additional labs include LH, testosterone, and DHEA-S; testosterone >200 ng/mL raises concern for androgen-producing ovarian/adrenal tumors (may be mildly elevated in PCOS), and DHEA-S >700 mcg/dL suggests an adrenal source (again, moderate elevations warrant high suspicion and thresholds are not required when a tumor is evident). An LH/FSH ratio >2 can be seen in PCOS but is not part of Rotterdam diagnostic criteria. Imaging is tailored to suspected cause: pelvic ultrasound for PCOS or ovarian tumor, abdominal CT for adrenal tumor, head MRI when indicated, and hysterosalpingography, sonohysterography, or diagnostic hysteroscopy when Asherman syndrome is suspected. Rare additional tests include serum transferrin (hemochromatosis), serum ACE (sarcoidosis), and karyotyping when POI occurs before age 40.
Treatment depends on the underlying cause and the patient’s goals (e.g., treating hirsutism or achieving pregnancy). Patients with hypogonadism should receive estrogen replacement plus calcium and vitamin D to prevent osteoporosis; those with a uterus also need continuous or intermittent progesterone to prevent endometrial hyperplasia or cancer, often using combined oral contraceptives. Many anatomic abnormalities require surgical correction; creation of a neovagina for Müllerian agenesis is usually delayed until emotional maturity and readiness for dilation or postoperative care, and if correction is not feasible, pregnancy may require a surrogate. Associated urogenital anomalies (e.g., renal agenesis) must be assessed and treated appropriately. In androgen insensitivity syndrome, gonadal malignancy risk is about 22% but rarely occurs before age 20; laparoscopic gonadectomy is performed after breast development and adult stature, and because there is no uterus, patients require estrogen only (no progesterone). Adult-onset CAH may be treated with low-dose corticosteroids plus sex steroids to reduce ACTH-driven androgen excess. Primary ovarian insufficiency requires estrogen and progesterone replacement, and conception typically requires IVF using donor oocytes; these patients have increased risk of osteoporosis and heart disease and may have autoimmune associations (hypothyroidism, Addison disease, diabetes), so fasting glucose, TSH, and (when appropriate) morning cortisol should be checked. If a Y chromosome is present, gonadal tissue removal is recommended at diagnosis to reduce tumor risk. Hypothyroidism is treated with thyroid replacement. Hyperprolactinemia is treated by stopping culprit drugs when possible and/or using dopamine agonists such as bromocriptine or cabergoline; surgery for pituitary adenomas is uncommon but may be needed for visual compromise, resistance to medical therapy, or rapid growth. Hypothalamic amenorrhea is treated by addressing the cause (behavioral modification and nutritional counseling for eating disorders/excess exercise; estrogen therapy and osteoporosis prevention for those who cannot reduce training), and infertility can be treated with clomiphene citrate, exogenous gonadotropins, or pulsatile GnRH therapy. For PCOS, primary therapy is weight loss with diet and exercise, with additional options including OCPs or cyclic progestins for endometrial protection, metformin to improve insulin resistance and ovulatory function (noting mixed effectiveness in recent studies), OCPs and/or spironolactone for hyperandrogenism, and ovulation induction with clomiphene citrate or letrozole. Asherman syndrome is treated with hysteroscopic lysis of adhesions followed by long-term exogenous estrogen to promote endometrial regrowth. A genetics consultation is appropriate for hereditary causes, and psychiatry consultation may be required for major depression, anorexia nervosa, bulimia nervosa, or other major psychiatric disorders.
Complications of amenorrhea include osteoporosis, endometrial hyperplasia and uterine cancer, and infertility. Prognosis depends on the underlying cause.
Patient and family education should include reassurance that amenorrhea itself is not automatically dangerous, but patients with an intact endometrium must understand the risks of unopposed estrogen (whether exogenous hormone therapy or endogenous estrogen exposure as in PCOS). Hypoestrogenic patients should be counseled on the importance of estrogen replacement to prevent bone loss, and the patient’s future fertility goals and potential for childbearing should be discussed.
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KembaraXtra-Medicine – Amebiasis
Amebiasis is an infection caused by the protozoal parasite Entamoeba histolytica. Although it primarily involves the colon, the disease may extend beyond the intestine, most notably causing amebic liver abscess, which is the most common and serious extraintestinal manifestation. When the intestinal infection is severe and associated with dysentery, it is also referred to as amebic dysentery. Amebiasis is classified under ICD-10CM codes A06.9 (amebiasis, unspecified), A06.1 (chronic intestinal amebiasis), and A06.7 (cutaneous amebiasis).
From an epidemiologic perspective, the incidence of amebiasis in the United States is approximately 1.2 cases per 100,000 population. Although relatively uncommon, it is clinically significant and occurs most frequently among institutionalized individuals, travelers to or immigrants from developing countries, and individuals engaging in oral–anal sexual practices. The estimated prevalence in the United States is about 4%, with approximately 80% of infections remaining asymptomatic. In contrast, in the developing world, amebiasis continues to be a major cause of morbidity and mortality, accounting for approximately 9% of all deaths in children younger than 5 years of age. The disease affects males and females equally overall; however, there is a marked male predominance in cases of amebic liver abscess. Amebiasis most commonly affects individuals in the second through sixth decades of life, with peak incidence noted in children aged 2 to 3 years and in adults older than 40 years.
The clinical presentation of amebiasis is often nonspecific, and many infected individuals remain asymptomatic. Approximately 20% of patients develop symptoms, most commonly diarrhea, which may be bloody, along with abdominal or back pain. In severe intestinal disease, abdominal tenderness is present in about 83% of cases, and fever occurs in approximately 38%. Patients with amebic liver abscess typically present with hepatomegaly, right upper quadrant abdominal tenderness, and fever, although these findings may be absent in fulminant disease.
The etiology of amebiasis involves infection with E. histolytica, while E. dispar and E. moshkovskii are more common but nonpathogenic species that are morphologically indistinguishable from E. histolytica. Transmission occurs through the fecal–oral route, and infection is highly contagious, requiring ingestion of only a small number of cysts in contaminated food or water. The infection is usually localized to the large intestine, particularly the cecum, where it may form a localized inflammatory mass known as an ameboma. In some cases, the organism invades the intestinal mucosa and gains access to the portal circulation, leading to extraintestinal disease. Important risk factors include travel to endemic regions, residence in institutions for the intellectually disabled, immunodeficiency, and male sex, particularly with respect to liver abscess formation.
The differential diagnosis of severe intestinal amebiasis includes ulcerative colitis and other forms of infectious enterocolitis, such as those caused by Shigella, Salmonella, Campylobacter, or invasive Escherichia coli. In elderly patients, ischemic colitis may present with a similar clinical picture and should also be considered.
The diagnostic workup focuses on stool-based testing and evaluation for extraintestinal disease. Stool antigen testing is more sensitive than routine ova and parasite examination for diagnosing amebiasis. Examination of three stool specimens collected over 7 to 10 days yields a sensitivity of 85% to 95%, although microscopy cannot reliably distinguish pathogenic from nonpathogenic species. Diagnostic yield can be improved by concentrating and staining specimens with Lugol iodine or methylene blue, and fecal leukocytes may or may not be present.
Laboratory testing includes fecal enzyme-linked immunosorbent assay (ELISA) antigen detection, which is specific for E. histolytica and has a sensitivity of approximately 87% and specificity greater than 90%. Polymerase chain reaction (PCR) assays on stool samples provide 90% to 95% sensitivity and 95% to 100% specificity. In selected cases, mucosal biopsy may be required to identify cysts or trophozoites. Serologic antibody tests are particularly useful in diagnosing extraintestinal disease, including liver abscess, although they may not distinguish recent from remote infection. Aspiration of abscess fluid is sometimes necessary to differentiate amebic from bacterial liver abscesses.
Imaging studies, including abdominal ultrasound or CT scanning, are essential for diagnosing amebic liver abscess and assessing its size, location, and potential complications.
Treatment is required for all patients infected with E. histolytica, regardless of symptom severity. Nonpathogenic Entamoeba species do not require therapy. Management of invasive disease typically begins with tinidazole, which is preferred for initial parasitic clearance, followed by an intraluminal amebicide such as paromomycin or diloxanide furoate to eradicate intestinal cysts. Metronidazole is an acceptable alternative to tinidazole for both intestinal disease and liver abscess. Amebic liver abscess generally responds well to medical therapy, but surgical intervention may be necessary in cases of toxic megacolon, impending rupture, or extension of the abscess into adjacent structures, including the pericardium.
Regarding disposition, host immunity after infection is incomplete, and reinfection rates are high in individuals who remain at risk. Referral to an infectious diseases specialist is recommended for patients with extraintestinal disease, persistent infection, or relapse. Surgical consultation is indicated for patients with toxic megacolon or complicated liver abscesses.
Important clinical considerations include the frequent coexistence of other intestinal parasites, particularly Giardia lamblia, and the high prevalence of nonpathogenic E. dispar colonization among homosexual men, which can complicate diagnosis. In the United States, E. histolytica remains the third most commonly isolated pathogen in returning travelers with infectious gastroenteritis, underscoring the importance of maintaining a high index of suspicion in appropriate clinical settings.
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KembaraXtra-Medicine – Amblyopia
Amblyopia refers to decreased vision in one or both eyes resulting from insufficient stimulation of the developing visual system during childhood. It occurs when normal visual development is disrupted, leading to reduced visual acuity that cannot be fully corrected with glasses alone. The most common causes are ocular misalignment (strabismus) and unequal refractive error between the eyes (anisometropia). Less commonly, amblyopia develops due to bilateral high refractive error (ametropic amblyopia) or visual deprivation, in which the ocular media are obstructed by conditions such as congenital cataract or severe ptosis.
Amblyopia is also known by several synonyms, including lazy eye, strabismic amblyopia, refractive amblyopia, occlusion amblyopia, and deprivation amblyopia (formerly called amblyopia ex anopsia). The condition is classified under multiple ICD-10CM codes, including unspecified amblyopia (H53.009), deprivation amblyopia (H53.01x), refractive amblyopia (H53.02x), and strabismic amblyopia (H53.03x), with laterality and bilaterality specified where applicable.
From an epidemiologic standpoint, amblyopia affects approximately 1% to 5% of the general population in the United States and represents the most common cause of decreased vision in children. It is responsible for permanent vision impairment in about 2.9% of adults. The condition is more common in premature infants, especially those born to drug-dependent mothers, and in neurologically impaired children. Additional risk factors include a family history of amblyopia, strabismus, or high refractive errors. There is no sex predilection, and the condition typically presents in early childhood, which is also the period of peak incidence.
The clinical presentation of amblyopia most often consists of reduced visual acuity in one eye despite appropriate corrective lenses, while the eye otherwise appears healthy on examination. In some cases, decreased vision may be associated with visible ocular abnormalities, such as a congenital cataract. Children may demonstrate a fixation preference, resisting occlusion of the better-seeing eye while tolerating coverage of the amblyopic eye, which is an important clinical clue.
The etiology of amblyopia includes refractive errors, strabismus, and visual deprivation caused by congenital cataract, corneal opacities, ptosis, or nystagmus. Rarely, amblyopia may result from prolonged occlusion due to patching or from systemic factors such as malnutrition or vitamin deficiency.
Diagnosis is best established through careful monocular visual acuity testing at the earliest possible age, generally around 3 years old. In preverbal or nonverbal children, photoscreening can help identify amblyopia or associated risk factors. Photoscreeners are increasingly available in primary care settings; however, clinicians should be aware that false-positive results are common, and abnormal findings require confirmation.
The differential diagnosis includes central nervous system causes such as cortical visual impairment, optic nerve disorders, corneal disease, retinal disorders, and, less commonly, malingering or secondary gain, such as a desire for glasses, which is reported more frequently in children, particularly girls.
The workup involves a complete eye examination to determine the underlying cause of reduced vision. Referral to an ophthalmologist is recommended for any child with visual acuity of 20/40 or worse in either eye, a two-line difference in visual acuity between the eyes, or failure of a photoscreening test in preverbal or nonverbal children. An ocular motility examination is essential to assess for strabismus. Laboratory testing is usually unnecessary, and imaging studies are generally not required unless a central nervous system abnormality is suspected.
Treatment depends on the age of the patient and the underlying etiology. Corrective glasses are used to address significant refractive errors and may help align the eyes in certain forms of strabismus. Penalization of the better-seeing eye, either by patching or atropine 1% eye drops, is the cornerstone of amblyopia therapy. The duration of treatment typically spans months and varies according to patient age, treatment response, and compliance. Younger children, especially those under 5 years of age, tend to respond more rapidly and completely, although some older children over 10 years of age who have never been treated may still show improvement.
Emerging therapies include digital or virtual reality–based dichoptic treatments, which aim to selectively stimulate the amblyopic eye. Although these technologies are under development and beginning to enter clinical use, there is no clear evidence that they are superior to traditional treatments, and they are often significantly more expensive. Surgical intervention is indicated in cases of deprivation amblyopia caused by conditions such as congenital cataract or severe congenital ptosis.
For chronic management, maintenance therapy with glasses, patching, or atropine may be required until the child reaches visual maturity, which typically occurs around 9 to 10 years of age. Continued monitoring during this period is essential to detect and prevent relapse.
Referral to an ophthalmologist is indicated whenever vision is compromised or amblyopia is suspected. Early specialist involvement improves diagnostic accuracy and treatment outcomes.
Important clinical pearls include the fact that earlier diagnosis leads to better outcomes, with the most robust treatment responses seen in children younger than 5 years. Nevertheless, treatment can still be beneficial in selected older children. Compliance with therapy is the single most important determinant of success. Recurrence is relatively common, with amblyopia returning in approximately 25% of children after patching is discontinued, underscoring the need for long-term follow-up.
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KembaraXtra-Medicine – Amyloidosis
Amyloid is an altered, insoluble protein folded in β-pleated sheets that is deposited extracellularly. Amyloid can accumulate in one or many organs, causing organ dysfunction. Amyloidosis refers to a heterogeneous group of disorders characterized by deposition of an amorphous, extracellular fibrillar protein in various organs and tissues. Subtypes include primary amyloidosis (AL), secondary amyloidosis (AA), hereditary amyloidosis, and localized amyloidosis. ICD-10CM codes include E85.0 (non-neuropathic heredofamilial), E85.1 (neuropathic heredofamilial), E85.2 (heredofamilial, unspecified), E85.3 (secondary systemic), E85.4 (organ-limited), E85.8 (other), and E85.9 (unspecified).
Amyloidosis nomenclature is based on the amyloid protein precursor and associated clinical features. AL or AH derives from immunoglobulin light or heavy chain and is primary or localized, often associated with myeloma or macroglobulinemia. AA derives from serum amyloid A (SAA) and occurs as secondary amyloidosis or with familial Mediterranean fever and other familial periodic fever syndromes. ATTR derives from transthyretin and is familial or senile. A fibrinogen derives from fibrinogen and is associated with familial renal amyloidosis (Ostertag type). Aβ2M derives from β2-microglobulin and is dialysis-associated, including carpal tunnel syndrome. Aβ derives from amyloid-β precursor protein (ABPP) and is associated with Alzheimer disease. Apo A-I/A-II–related forms include apolipoprotein A-I (proteinuria) and apolipoprotein A-II (cardiac and neuropathy patterns). A lysozyme involves lysozyme deposition affecting the GI tract, liver, and kidneys. ALECT2 is noted as a renal form (leukocyte chemotactic factor 2 amyloidosis).
A major classification system (not exhaustive) includes: AA (serum amyloid A) causing systemic amyloidosis, often predominantly renal, linked to acquired or hereditary chronic inflammatory disease (formerly “secondary/reactive”); AL (monoclonal immunoglobulin light chains) causing systemic amyloidosis potentially involving many organs and associated with myeloma/monoclonal gammopathy/occult B-cell dyscrasias (formerly “primary”); and ATTR wild-type (normal plasma transthyretin) causing nonhereditary systemic amyloidosis with predominantly cardiac involvement (formerly “senile cardiac amyloidosis”). ATTR variant (genetic variants such as ATTR Met30, Ala60, Ile122) can cause familial amyloid polyneuropathy (FAP) often with prominent cardiomyopathy, and certain mutations (e.g., TTR Ile122) may produce predominantly cardiac involvement without neuropathy. Aβ2M (β2-microglobulin) causes dialysis-related amyloidosis with renal failure and long-term dialysis, with predominantly articular/periarticular involvement. Aβ causes cerebrovascular and intracerebral plaque amyloid in Alzheimer disease and may be familial. AApoAI (genetic variants of apolipoprotein AI) causes autosomal dominant systemic amyloidosis, typically nonneuropathic with visceral involvement—especially nephropathy—and minor wild-type deposits can occur in the aorta with aging. AApoAII causes autosomal dominant systemic amyloidosis with predominantly renal involvement. AFib (fibrinogen A α-chain variants) causes autosomal dominant systemic amyloidosis with nonneuropathic predominant nephropathy. ALys (lysozyme variants) causes autosomal dominant systemic amyloidosis with predominantly renal and GI involvement and can rarely present with hepatic rupture. ACys (cystatin C variant) is linked to hereditary cerebral hemorrhage with cerebral and systemic amyloidosis in Icelandic individuals. AGel (gelsolin variants) causes autosomal dominant systemic amyloidosis with predominantly cranial nerve involvement plus lattice corneal dystrophy and is described as most common in Finland.
In the United States, incidence is estimated at 1500–3500 new cases annually, with AL being the most common type. Amyloidosis primarily affects men ages 60–70 years. Common presenting symptoms include fatigue, dyspnea, edema, paresthesias, and weight loss, and other findings depend on organ involvement. Diagnosis should be considered in patients with a multisystem disorder involving the heart, kidney, liver, or nervous system. Renal involvement may present with nephrotic syndrome. Pulmonary involvement may cause fatigue and dyspnea. GI involvement is uncommon but may present with diarrhea, nausea, abdominal pain, and macroglossia. Cardiac involvement produces an infiltrative cardiomyopathy with preserved ejection fraction and diastolic dysfunction; in transthyretin-related disease, transthyretin dissociation leads to deposition of misfolded monomers as amyloid fibrils in the myocardium with subsequent cardiomyopathy and heart failure. Patients may have bleeding problems from factor X deficiency or fragile vessels infiltrated by amyloid; periorbital bleeding (“raccoon eyes”) is characteristic. Nervous system involvement can cause peripheral neuropathy, tendinopathy, muscle weakness, numbness, syncope, or dizziness, and associated autonomic neuropathy can be severely disabling. Syndromes in primary (AL) amyloidosis include nephrotic/nephrotic with renal failure (30%), hepatomegaly (24%), congestive heart failure (22%), carpal tunnel (21%), neuropathy (17%), and orthostatic hypotension (12%).
The common mechanism is deposition of Congo red–staining amyloid fibrils, but key subtype differences exist. AL is associated with an underlying clonal plasma cell disorder producing abnormal light chains with possible multi-organ deposition. AA has no plasma cell disorder and results from long-standing systemic inflammation (examples listed include tuberculosis, leprosy, malaria, untreated syphilis). Localized amyloidosis results from localized fibril synthesis without a plasma cell disorder. Familial amyloidosis includes forms due to transthyretin gene (TTR) mutations, with hepatocyte-derived transthyretin deposition in peripheral nerves and the heart.
Differential diagnosis depends on organ involvement. For renal disease consider toxin- or drug-induced necrosis, glomerulonephritis, renal vein thrombosis. For pulmonary disease consider sarcoidosis, connective tissue disease, infectious causes. For restrictive cardiomyopathy consider endomyocardial fibrosis or viral myocarditis. For carpal tunnel consider rheumatoid arthritis, hypothyroidism, overuse. For peripheral neuropathy consider alcohol abuse, vitamin deficiencies, diabetes mellitus.
Workup includes blood and urine testing for abnormal light chains, tests for target-organ damage, and histologic confirmation. Typical confirmation is via fat pad aspiration and bone marrow biopsy with Congo red staining. Recommended diagnostic evaluation includes CBC; chemistries and other labs (sodium, potassium, alkaline phosphatase, calcium, phosphorus, AST, bilirubin, creatinine, β2-microglobulin, glucose, cholesterol, uric acid, thyroid profile); serum and urine immunofixation; assays for immunoglobulin free light chains and immunoglobulins G, A, and M; cardiac markers (troponin, NT-proBNP); coagulation evaluation (factor X and prothrombin time); and cardiac/pulmonary assessment with chest x-ray, ECG, and echocardiogram with Doppler and strain imaging. Amyloid staging assigns 1 point each for FLC-diff ≥18 mg/dL, cTnT ≥0.025 ng/mL, and NT-proBNP ≥1800 pg/mL, producing stages I–IV (scores 0–3). Reported median survival (months) by stage is 94.1, 40.3, 14, and 5.8, respectively. Laboratory testing also includes SPEP/UPEP with immunofixation for light chains, routine labs such as BUN/creatinine, liver function tests, thyroid function, urine albumin, and biopsy confirmation; if fat pad biopsy is negative, biopsy of the affected organ may be required.
Imaging can help define organ involvement. Cardiac MRI may show a distinctive pattern. Two-dimensional Doppler echocardiography is useful for cardiac evaluation but is less sensitive than cardiac MRI. Nuclear imaging with technetium-labeled aprotinin may detect cardiac amyloidosis. Labeled diphosphonates are important for typing amyloidosis and diagnosing heart involvement in transthyretin cardiac amyloidosis, and bone scintigraphy may detect cardiac involvement earlier than echocardiography in transthyretin patients. Serum amyloid P (SAP) scintigraphy has high sensitivity for detecting deposits in liver, spleen, kidneys, adrenal glands, bones.
Acute/general management and disease-directed therapy depend on subtype and organ involvement. Patients with AL amyloidosis should be evaluated for autologous hematopoietic stem cell transplantation (HSCT); good candidates include those with good performance status, age <70, and limited organ involvement. tafamidis is an oral transthyretin stabilizer fda approved for adults with transthyretin-mediated amyloid cardiomyopathy (attr-cm) has been shown to decrease hospitalizations deaths in attr-cm. al, chemotherapy aims reduce production of amyloidogenic light chains by targeting clonal plasma cells; agents used multiple myeloma are effective, including melphalan prednisone, imids (thalidomide, lenalidomide) proteasome inhibitors also used. patients ineligible autologous hsct should receive melphalan- or bortezomib-based regimens. trials oligonucleotide drugs (inotersen, patisiran) have improvement clinical manifestations hereditary amyloidosis. who develop renal failure may require hemodialysis transplant. liver transplantation successfully familial secondary (aa) amyloidosis, recognition treatment the underlying disorder needed. newly diagnosed al show that adding daratumumab bortezomib, cyclophosphamide, dexamethasone associated higher hematologic complete response rates.< />pan>
Major treatment options include, for AL amyloidosis, IV melphalan with autologous stem cell rescue (G-CSF mobilized peripheral blood stem cell collection, IV melphalan 140–200 mg/m², autologous stem cell reinfusion), cyclic oral melphalan and dexamethasone (melphalan 0.22 mg/kg/day ×4 days; dexamethasone 20–40 mg/day ×4 days or weekly; repeat every 4 weeks), immunomodulators (lenalidomide 5–15 mg/day ×21 days with dexamethasone 20–40 mg weekly; repeat every 4 weeks), and proteasome inhibitors (IV bortezomib 0.7–1.6 mg/m² 1–2 times per week; repeat every 3–5 weeks). For AA amyloidosis, options include aggressive treatment of underlying inflammatory disease, medical or surgical treatment of infection, colchicine 1.2–1.8 mg/day for AA secondary to familial Mediterranean fever, and investigational antifibril drug eprodisate. For ATTR, options include orthotopic liver transplantation, transthyretin stabilizers (tafamidis, investigational diflunisal), and investigational oligonucleotide drugs (inotersen, patisiran).
Supportive treatment across all amyloidosis types is symptom- and organ-directed. For cardiac congestive failure, options include salt restriction 1–2 g/day and diuretics (furosemide, spironolactone, metolazone). For arrhythmias, consider pacemaker, automatic implantable cardiac defibrillator, and antiarrhythmics. For renal nephrotic syndrome, use salt restriction 1–2 g/day, elastic stockings and leg elevation, maintaining dietary protein, and an ACE inhibitor if blood pressure tolerates. For renal failure, use dialysis (long-term ambulatory peritoneal dialysis or hemodialysis). For autonomic nervous system orthostatic hypotension, options include midodrine, increased dietary salt or fludrocortisone depending on edema, and elastic stockings. For gastric atony/ileus, use small frequent low-fat feedings (6/day), oral nutritional supplements, jejunostomy tube feeding, or parenteral nutrition. For GI diarrhea, options include a low-fat diet (≤40 g), psyllium, loperamide, tincture of opium, and parenteral nutrition. For macroglossia, use a soft solid diet; partial glossectomy is rarely effective. For peripheral sensory neuropathy, avoid trauma and use medications such as gabapentin 100–300 mg three times daily, amitriptyline 25–50 mg at bedtime, or pregabalin 50–100 mg three times daily. For motor neuropathy with footdrop, use ankle-foot orthotics and physical therapy. For hematologic issues with intracutaneous bleeding, avoid trauma and antiplatelet agents; for factor X deficiency, use factor replacement (recombinant factor VIIa, prothrombin complex concentrates). Splenectomy may be considered for splenomegaly.
Prognosis is determined primarily by cardiac involvement and the amyloidosis form. In endomyocardial biopsy–documented cardiac amyloidosis, longer-term survival correlates more strongly with NYHA functional class than with ECG or echocardiographic variables. In AA amyloidosis, eradication of the predisposing disease slows and can occasionally reverse progression, with a median survival after diagnosis of 133 months. Patients with familial amyloidotic polyneuropathy often have a prolonged course of 10–15 years. Dialysis-associated amyloidosis progression can be improved with newer dialysis membranes that pass β2-microglobulin. Median survival in patients with overt congestive heart failure is approximately 6 months, compared with 30 months without CHF.
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KembaraXtra-Medicine- Ankylosing Spondylitis
Basic Information and Definition
Ankylosing spondylitis (AS) is a chronic inflammatory arthritis that primarily affects the sacroiliac joints and axial skeleton. It is characterized by ankylosis, which is abnormal joint stiffening, and enthesitis, inflammation at tendon and ligament insertion sites. Ankylosing spondylitis belongs to the family of seronegative spondyloarthropathies, which also includes reactive arthritis, psoriatic spondylitis, and enteropathic arthritis.
Synonyms
Ankylosing spondylitis is also known as Marie-Strümpell disease and Bechterew disease.
ICD-10-CM Codes
Ankylosing spondylitis is coded according to the region of spinal involvement, including unspecified spinal sites, juvenile ankylosing spondylitis, and specific cervical, thoracic, lumbar, lumbosacral, sacral, and occipito-atlanto-axial regions.
Epidemiology and Demographics
The prevalence of ankylosing spondylitis ranges from 0.1% to 1% of the general population and varies by ethnicity and the prevalence of the HLA-B27 allele. In populations with HLA-B27 positivity, prevalence is significantly higher, especially among individuals with a family history of spondyloarthropathy. The disease predominantly affects males, with approximately 70% of cases occurring in men. Symptoms typically begin between ages 15 and 35, and most patients develop symptoms before age 45.
Physical Findings and Clinical Presentation
Patients commonly present with chronic inflammatory back pain of insidious onset lasting longer than three months. Morning stiffness lasting at least 30 minutes is typical and improves with physical activity but worsens with rest. Bilateral sacroiliac joint tenderness is common, along with limited lumbar spine mobility. Enthesitis frequently affects the Achilles tendon and plantar fascia. Reduced chest expansion may occur due to costovertebral joint involvement. Peripheral arthritis, usually asymmetric and affecting the lower extremities, may be present. In advanced disease, patients may develop a characteristic posture with loss of lumbar lordosis, fixed hip flexion, knee flexion, and compensatory hyperextension of the neck. Extra-articular manifestations include acute anterior uveitis or iritis, seen in up to 40% of patients, as well as cardiovascular involvement such as aortic insufficiency, pulmonary fibrosis, and increased risk of osteoporosis.
Inflammatory Back Pain Characteristics
Inflammatory back pain in ankylosing spondylitis typically begins before age 45, persists for more than three months, and is localized to the lower back with possible alternating buttock pain. Symptoms often awaken patients during the second half of the night and improve with exercise or nonsteroidal anti-inflammatory drugs, but not with rest.
Etiology and Pathogenesis
The exact cause of ankylosing spondylitis remains incompletely understood. Genetic susceptibility plays a major role, with HLA-B27 being the strongest known predisposing factor. Immune dysregulation, environmental triggers, infections such as Klebsiella pneumoniae, and hormonal influences may contribute to disease development. Tumor necrosis factor (TNF) and other inflammatory cytokines are central mediators of the inflammatory process.
Diagnosis
Diagnosis is based on clinical features, laboratory findings, and imaging. Demonstration of inflammatory sacroiliitis on imaging is diagnostic in most patients, although some meet criteria for nonradiographic axial spondyloarthritis. Elevated erythrocyte sedimentation rate and C-reactive protein may be present, along with mild anemia. HLA-B27 testing supports the diagnosis in appropriate clinical contexts but is not diagnostic on its own, as it is present in a proportion of the healthy population.
Differential Diagnosis
The differential diagnosis includes diffuse idiopathic skeletal hyperostosis, mechanical or noninflammatory back pain, and other inflammatory spondyloarthropathies such as psoriatic arthritis, reactive arthritis, and enteropathic arthritis.
Imaging Studies
Pelvic radiographs classically demonstrate bilateral sacroiliitis and are part of the modified New York criteria. As disease progresses, vertebral bodies lose their normal concavity and become squared, with calcification of spinal ligaments leading to the characteristic bamboo spine appearance. Advanced disease may show diskovertebral erosions known as Andersson lesions. MRI is particularly useful in early disease and can detect active inflammation, bone marrow edema, erosions, and sacroiliitis before changes are visible on plain radiographs.
Nonpharmacologic Treatment
Regular exercise is a cornerstone of management, with emphasis on maintaining spinal mobility, posture, and aerobic fitness. Patients should be instructed in spinal extension and postural exercises to prevent flexion deformities. Sleeping supine on a firm mattress without pillows under the head or knees is recommended. Breathing exercises help preserve chest expansion.
Pharmacologic Therapy
Continuous full-dose NSAIDs are first-line therapy and are effective in controlling pain and stiffness; indomethacin may be particularly effective in some patients. Sulfasalazine may benefit patients with significant peripheral arthritis. Biologic therapies targeting TNF, such as etanercept, infliximab, and adalimumab, are highly effective for patients with inadequate response to NSAIDs and improve symptoms, spinal mobility, and quality of life. Etanercept is generally avoided in patients with recurrent uveitis. Interleukin-17 inhibitors, including secukinumab and ixekizumab, are approved alternatives for active disease.
Disposition and Prognosis
Most patients with ankylosing spondylitis have a normal life expectancy; however, many experience progressive loss of spinal mobility and functional impairment. Early diagnosis and appropriate therapy significantly improve long-term outcomes.
Referral
All patients with suspected or confirmed ankylosing spondylitis should be referred to a rheumatologist for comprehensive evaluation and long-term management.
Pearls and Considerations
A positive family history increases the diagnostic value of HLA-B27 testing. Selected patients with severe spinal deformities may benefit from corrective osteotomy. Emerging evidence suggests an increased risk of cardiovascular and vascular mortality, particularly in men with longstanding disease.
Basic Information and Definition
Ankylosing spondylitis (AS) is a chronic inflammatory arthritis that primarily affects the sacroiliac joints and axial skeleton. It is characterized by ankylosis, which is abnormal joint stiffening, and enthesitis, inflammation at tendon and ligament insertion sites. Ankylosing spondylitis belongs to the family of seronegative spondyloarthropathies, which also includes reactive arthritis, psoriatic spondylitis, and enteropathic arthritis.
Synonyms
Ankylosing spondylitis is also known as Marie-Strümpell disease and Bechterew disease.
ICD-10-CM Codes
Ankylosing spondylitis is coded according to the region of spinal involvement, including unspecified spinal sites, juvenile ankylosing spondylitis, and specific cervical, thoracic, lumbar, lumbosacral, sacral, and occipito-atlanto-axial regions.
Epidemiology and Demographics
The prevalence of ankylosing spondylitis ranges from 0.1% to 1% of the general population and varies by ethnicity and the prevalence of the HLA-B27 allele. In populations with HLA-B27 positivity, prevalence is significantly higher, especially among individuals with a family history of spondyloarthropathy. The disease predominantly affects males, with approximately 70% of cases occurring in men. Symptoms typically begin between ages 15 and 35, and most patients develop symptoms before age 45.
Physical Findings and Clinical Presentation
Patients commonly present with chronic inflammatory back pain of insidious onset lasting longer than three months. Morning stiffness lasting at least 30 minutes is typical and improves with physical activity but worsens with rest. Bilateral sacroiliac joint tenderness is common, along with limited lumbar spine mobility. Enthesitis frequently affects the Achilles tendon and plantar fascia. Reduced chest expansion may occur due to costovertebral joint involvement. Peripheral arthritis, usually asymmetric and affecting the lower extremities, may be present. In advanced disease, patients may develop a characteristic posture with loss of lumbar lordosis, fixed hip flexion, knee flexion, and compensatory hyperextension of the neck. Extra-articular manifestations include acute anterior uveitis or iritis, seen in up to 40% of patients, as well as cardiovascular involvement such as aortic insufficiency, pulmonary fibrosis, and increased risk of osteoporosis.
Inflammatory Back Pain Characteristics
Inflammatory back pain in ankylosing spondylitis typically begins before age 45, persists for more than three months, and is localized to the lower back with possible alternating buttock pain. Symptoms often awaken patients during the second half of the night and improve with exercise or nonsteroidal anti-inflammatory drugs, but not with rest.
Etiology and Pathogenesis
The exact cause of ankylosing spondylitis remains incompletely understood. Genetic susceptibility plays a major role, with HLA-B27 being the strongest known predisposing factor. Immune dysregulation, environmental triggers, infections such as Klebsiella pneumoniae, and hormonal influences may contribute to disease development. Tumor necrosis factor (TNF) and other inflammatory cytokines are central mediators of the inflammatory process.
Diagnosis
Diagnosis is based on clinical features, laboratory findings, and imaging. Demonstration of inflammatory sacroiliitis on imaging is diagnostic in most patients, although some meet criteria for nonradiographic axial spondyloarthritis. Elevated erythrocyte sedimentation rate and C-reactive protein may be present, along with mild anemia. HLA-B27 testing supports the diagnosis in appropriate clinical contexts but is not diagnostic on its own, as it is present in a proportion of the healthy population.
Differential Diagnosis
The differential diagnosis includes diffuse idiopathic skeletal hyperostosis, mechanical or noninflammatory back pain, and other inflammatory spondyloarthropathies such as psoriatic arthritis, reactive arthritis, and enteropathic arthritis.
Imaging Studies
Pelvic radiographs classically demonstrate bilateral sacroiliitis and are part of the modified New York criteria. As disease progresses, vertebral bodies lose their normal concavity and become squared, with calcification of spinal ligaments leading to the characteristic bamboo spine appearance. Advanced disease may show diskovertebral erosions known as Andersson lesions. MRI is particularly useful in early disease and can detect active inflammation, bone marrow edema, erosions, and sacroiliitis before changes are visible on plain radiographs.
Nonpharmacologic Treatment
Regular exercise is a cornerstone of management, with emphasis on maintaining spinal mobility, posture, and aerobic fitness. Patients should be instructed in spinal extension and postural exercises to prevent flexion deformities. Sleeping supine on a firm mattress without pillows under the head or knees is recommended. Breathing exercises help preserve chest expansion.
Pharmacologic Therapy
Continuous full-dose NSAIDs are first-line therapy and are effective in controlling pain and stiffness; indomethacin may be particularly effective in some patients. Sulfasalazine may benefit patients with significant peripheral arthritis. Biologic therapies targeting TNF, such as etanercept, infliximab, and adalimumab, are highly effective for patients with inadequate response to NSAIDs and improve symptoms, spinal mobility, and quality of life. Etanercept is generally avoided in patients with recurrent uveitis. Interleukin-17 inhibitors, including secukinumab and ixekizumab, are approved alternatives for active disease.
Disposition and Prognosis
Most patients with ankylosing spondylitis have a normal life expectancy; however, many experience progressive loss of spinal mobility and functional impairment. Early diagnosis and appropriate therapy significantly improve long-term outcomes.
Referral
All patients with suspected or confirmed ankylosing spondylitis should be referred to a rheumatologist for comprehensive evaluation and long-term management.
Pearls and Considerations
A positive family history increases the diagnostic value of HLA-B27 testing. Selected patients with severe spinal deformities may benefit from corrective osteotomy. Emerging evidence suggests an increased risk of cardiovascular and vascular mortality, particularly in men with longstanding disease.
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KembaraXtra-Medicine- Anorectal Fistula
Basic Information and Definition
An anorectal fistula is an inflammatory tract that connects the anal canal to the perianal skin. It has a primary (internal) opening in the anal canal at the dentate line and a secondary (external) opening on the perianal skin. Most fistulae develop as a complication of a perianal abscess that begins with infection of an anal crypt gland; if the abscess ruptures and the tract becomes epithelialized, a chronic fistula forms.
Classification by Relationship to the Anal Sphincter Complex
Intersphincteric fistulas are the most common and travel within the intersphincteric plane to the perianal skin. Transsphincteric fistulas are frequent and pass from the internal opening through both internal and external sphincters into the ischiorectal fossa and then to the perianal skin. Suprasphincteric fistulas are uncommon; after traversing the internal sphincter, the tract courses above the puborectalis and then descends lateral to the external sphincter into the ischiorectal space, sometimes associated with a supralevator abscess if the cavity extends upward. Extrasphincteric fistulas are rare and pass from the rectum above the levators, through the levator muscles, and into the ischiorectal space and perianal skin. Submucosal fistulas originate at the dentate line from an infected crypt without involving the sphincter muscles. Horseshoe fistulas extend from one ischiorectal fossa to the other behind the rectum. (Fistulotomy is not appropriate for extrasphincteric fistulas because of the high risk of incontinence.)
Synonyms
Fistula-in-ano and anal fistula.
ICD-10-CM Codes
K60.5 (Anorectal fistula) and K60.3 (Anal fistula).
Epidemiology and Demographics
Anorectal fistulas occur across all ages, with an average age around 39 years. They are about twice as common in men as in women. They are associated with inflammatory bowel disease and constipation. In pediatrics, they are more common in infants, with boys affected more than girls.
Physical Findings and Clinical Presentation
In the acute stage, patients may have perianal swelling, pain with defecation and sitting, and fever. In the chronic stage, symptoms include persistent pain, malodorous perianal drainage or bleeding, and anal pruritus. The external opening is often tender and inflamed, typically within 2–3 cm of the anal verge, and may express purulent or serosanguineous drainage with compression. A greater distance from the anal margin increases the likelihood of a more complex fistula with upward extension. Recurrent perianal abscess strongly suggests an underlying fistula.
Goodsall Rule
The likely course of the fistula tract can often be estimated from the external opening location. If the external opening is anterior to an imaginary transverse line through the midpoint of the anus, the tract usually runs radially to the anal canal. If the opening is posterior to that line, the tract is usually curved and enters the anal canal at the posterior midline. An important exception is an anterior external opening more than 3 cm from the anus, which may still curve posteriorly and open in the posterior midline.
Etiology
The most common cause is a nonspecific infection of an anal crypt gland involving skin or intestinal flora, and fistulas are more likely when intestinal microorganisms are cultured from the initial abscess. Other infectious causes include tuberculosis, lymphogranuloma venereum, and actinomycosis. Inflammatory bowel disease (especially Crohn disease, and less commonly ulcerative colitis) is an important cause. Trauma can lead to fistulas, including after surgery (e.g., episiotomy, prostatectomy), foreign bodies, or anal intercourse. Malignancy (carcinoma, leukemia, lymphoma) and malignancy treatment (surgery, radiation) can also cause fistula formation.
Diagnosis
Diagnosis is commonly established by history and physical examination, especially in simple fistulas, supported by anoscopy and/or further evaluation when needed.
Differential Diagnosis
Anal abscess, anal ulcer or fissure, hidradenitis suppurativa, pilonidal sinus, Bartholin gland abscess or sinus, and infected perianal sebaceous cysts.
Workup
Digital rectal examination is performed to assess sphincter tone and voluntary squeeze pressure, detect an extraluminal mass, identify an indurated tract, and attempt to palpate an internal opening or pit. Gentle probing of the external opening may be performed but should be done carefully to avoid creating a false tract; about half of patients may not have a clinically detectable internal opening. Exam alone may be sufficient for many simple fistulas. Anoscopy is used to evaluate the anal canal. Proctosigmoidoscopy is recommended to exclude inflammatory or neoplastic disease. When extensive evaluation or procedures are required, studies should be done under adequate anesthesia.
Laboratory Tests
A complete blood count may be obtained. Rectal biopsy is appropriate if inflammatory bowel disease or malignancy is suspected; biopsy of the external orifice is not useful.
Imaging Studies
Transanal endosonography (EUS) can help estimate how much sphincter would be divided during fistulotomy and can detect undrained sepsis, complex anatomy, and high blind tracts. MRI is useful for identifying suprasphincteric or extrasphincteric tracts, and MRI/EUS are generally more accurate than clinical exam in mapping fistula anatomy. CT is limited because it lacks the resolution to define tract relationships to sphincters and levators. Fistulography is rarely needed now. Colonoscopy or barium enema should be considered when IBD or malignancy is suspected, when fistulas are recurrent or multiple, or in patients younger than 25 years. A small bowel series may occasionally be obtained for similar indications.
Treatment: Nonpharmacologic
Sitz baths can provide symptomatic relief and improve comfort.
Pharmacologic Therapy
Medications are rarely recommended as primary therapy. Immunomodulators such as infliximab may be used in selected cases, particularly when fistulas are related to Crohn disease.
Acute General Management
Surgery is the treatment of choice. Broad-spectrum antibiotics are used when cellulitis is present, when the patient is immunocompromised, or when valvular heart disease or prosthetic devices are present. Stool softeners or laxatives may be used to reduce straining and discomfort.
Chronic Management and Surgical Options
Definitive management is typically surgical, tailored to fistula type and complexity. The main goals are to eradicate the fistula, prevent recurrence, preserve sphincter function, and minimize healing time. Surgical and procedural options include fistulotomy, fistulectomy, seton placement (to maintain drainage while healing occurs), fibrin glue, fistula plugs, LIFT procedure (ligation of the intersphincteric fistula tract), rectal advancement flaps, and, in select complex situations, colostomy. Strategy varies by classification; superficial/intersphincteric and low transsphincteric fistulas are often candidates for fistulotomy, while higher or more complex fistulas more often require sphincter-sparing approaches such as setons, LIFT, advancement flaps, glue, or plugs. Extrasphincteric disease requires addressing any intraabdominal or pelvic source and is not managed with fistulotomy due to incontinence risk.
Disposition
Most patients are managed with outpatient surgery.
Referral
Referral to a surgeon experienced in anorectal fistula management is recommended.
Pearls and Considerations
HIV-positive and diabetic patients who develop perirectal abscesses or fistulas should be treated as true surgical emergencies. The risk of septicemia, Fournier gangrene, and other severe septic complications makes rapid evaluation and drainage imperative.
Basic Information and Definition
An anorectal fistula is an inflammatory tract that connects the anal canal to the perianal skin. It has a primary (internal) opening in the anal canal at the dentate line and a secondary (external) opening on the perianal skin. Most fistulae develop as a complication of a perianal abscess that begins with infection of an anal crypt gland; if the abscess ruptures and the tract becomes epithelialized, a chronic fistula forms.
Classification by Relationship to the Anal Sphincter Complex
Intersphincteric fistulas are the most common and travel within the intersphincteric plane to the perianal skin. Transsphincteric fistulas are frequent and pass from the internal opening through both internal and external sphincters into the ischiorectal fossa and then to the perianal skin. Suprasphincteric fistulas are uncommon; after traversing the internal sphincter, the tract courses above the puborectalis and then descends lateral to the external sphincter into the ischiorectal space, sometimes associated with a supralevator abscess if the cavity extends upward. Extrasphincteric fistulas are rare and pass from the rectum above the levators, through the levator muscles, and into the ischiorectal space and perianal skin. Submucosal fistulas originate at the dentate line from an infected crypt without involving the sphincter muscles. Horseshoe fistulas extend from one ischiorectal fossa to the other behind the rectum. (Fistulotomy is not appropriate for extrasphincteric fistulas because of the high risk of incontinence.)
Synonyms
Fistula-in-ano and anal fistula.
ICD-10-CM Codes
K60.5 (Anorectal fistula) and K60.3 (Anal fistula).
Epidemiology and Demographics
Anorectal fistulas occur across all ages, with an average age around 39 years. They are about twice as common in men as in women. They are associated with inflammatory bowel disease and constipation. In pediatrics, they are more common in infants, with boys affected more than girls.
Physical Findings and Clinical Presentation
In the acute stage, patients may have perianal swelling, pain with defecation and sitting, and fever. In the chronic stage, symptoms include persistent pain, malodorous perianal drainage or bleeding, and anal pruritus. The external opening is often tender and inflamed, typically within 2–3 cm of the anal verge, and may express purulent or serosanguineous drainage with compression. A greater distance from the anal margin increases the likelihood of a more complex fistula with upward extension. Recurrent perianal abscess strongly suggests an underlying fistula.
Goodsall Rule
The likely course of the fistula tract can often be estimated from the external opening location. If the external opening is anterior to an imaginary transverse line through the midpoint of the anus, the tract usually runs radially to the anal canal. If the opening is posterior to that line, the tract is usually curved and enters the anal canal at the posterior midline. An important exception is an anterior external opening more than 3 cm from the anus, which may still curve posteriorly and open in the posterior midline.
Etiology
The most common cause is a nonspecific infection of an anal crypt gland involving skin or intestinal flora, and fistulas are more likely when intestinal microorganisms are cultured from the initial abscess. Other infectious causes include tuberculosis, lymphogranuloma venereum, and actinomycosis. Inflammatory bowel disease (especially Crohn disease, and less commonly ulcerative colitis) is an important cause. Trauma can lead to fistulas, including after surgery (e.g., episiotomy, prostatectomy), foreign bodies, or anal intercourse. Malignancy (carcinoma, leukemia, lymphoma) and malignancy treatment (surgery, radiation) can also cause fistula formation.
Diagnosis
Diagnosis is commonly established by history and physical examination, especially in simple fistulas, supported by anoscopy and/or further evaluation when needed.
Differential Diagnosis
Anal abscess, anal ulcer or fissure, hidradenitis suppurativa, pilonidal sinus, Bartholin gland abscess or sinus, and infected perianal sebaceous cysts.
Workup
Digital rectal examination is performed to assess sphincter tone and voluntary squeeze pressure, detect an extraluminal mass, identify an indurated tract, and attempt to palpate an internal opening or pit. Gentle probing of the external opening may be performed but should be done carefully to avoid creating a false tract; about half of patients may not have a clinically detectable internal opening. Exam alone may be sufficient for many simple fistulas. Anoscopy is used to evaluate the anal canal. Proctosigmoidoscopy is recommended to exclude inflammatory or neoplastic disease. When extensive evaluation or procedures are required, studies should be done under adequate anesthesia.
Laboratory Tests
A complete blood count may be obtained. Rectal biopsy is appropriate if inflammatory bowel disease or malignancy is suspected; biopsy of the external orifice is not useful.
Imaging Studies
Transanal endosonography (EUS) can help estimate how much sphincter would be divided during fistulotomy and can detect undrained sepsis, complex anatomy, and high blind tracts. MRI is useful for identifying suprasphincteric or extrasphincteric tracts, and MRI/EUS are generally more accurate than clinical exam in mapping fistula anatomy. CT is limited because it lacks the resolution to define tract relationships to sphincters and levators. Fistulography is rarely needed now. Colonoscopy or barium enema should be considered when IBD or malignancy is suspected, when fistulas are recurrent or multiple, or in patients younger than 25 years. A small bowel series may occasionally be obtained for similar indications.
Treatment: Nonpharmacologic
Sitz baths can provide symptomatic relief and improve comfort.
Pharmacologic Therapy
Medications are rarely recommended as primary therapy. Immunomodulators such as infliximab may be used in selected cases, particularly when fistulas are related to Crohn disease.
Acute General Management
Surgery is the treatment of choice. Broad-spectrum antibiotics are used when cellulitis is present, when the patient is immunocompromised, or when valvular heart disease or prosthetic devices are present. Stool softeners or laxatives may be used to reduce straining and discomfort.
Chronic Management and Surgical Options
Definitive management is typically surgical, tailored to fistula type and complexity. The main goals are to eradicate the fistula, prevent recurrence, preserve sphincter function, and minimize healing time. Surgical and procedural options include fistulotomy, fistulectomy, seton placement (to maintain drainage while healing occurs), fibrin glue, fistula plugs, LIFT procedure (ligation of the intersphincteric fistula tract), rectal advancement flaps, and, in select complex situations, colostomy. Strategy varies by classification; superficial/intersphincteric and low transsphincteric fistulas are often candidates for fistulotomy, while higher or more complex fistulas more often require sphincter-sparing approaches such as setons, LIFT, advancement flaps, glue, or plugs. Extrasphincteric disease requires addressing any intraabdominal or pelvic source and is not managed with fistulotomy due to incontinence risk.
Disposition
Most patients are managed with outpatient surgery.
Referral
Referral to a surgeon experienced in anorectal fistula management is recommended.
Pearls and Considerations
HIV-positive and diabetic patients who develop perirectal abscesses or fistulas should be treated as true surgical emergencies. The risk of septicemia, Fournier gangrene, and other severe septic complications makes rapid evaluation and drainage imperative.
- Published on
KembaraXtra-Medicine- Anorectal Stricture
Basic Information and Definition
An anorectal stricture, also referred to as anal stenosis, is an abnormal narrowing of the anal canal. Strictures are classified according to both severity and location. Severity ranges from mild, in which a well-lubricated finger or medium Hill-Ferguson retractor can pass easily, to moderate, where passage is possible only with forceful dilation, and severe, where no passage is possible. Location is described as low (at least 0.5 cm distal to the dentate line), middle (within 0.5 cm on either side of the dentate line), or high (at least 0.5 cm proximal to the dentate line).
Synonyms and Coding
Anorectal stricture is also known as anal stenosis or Küss disease. The ICD-10-CM code used is K62.4, which denotes stenosis of the anus and rectum.
Epidemiology and Risk Factors
Hemorrhoid surgery is the most common overall cause of anorectal stricture, occurring in approximately 5% to 10% of patients after radical hemorrhoidectomy, particularly for grade III and IV hemorrhoidal disease. The risk of developing a stricture is directly related to the extent of anoderm resection. Other important risk factors include prior anorectal surgery, inflammatory bowel disease, previous pelvic radiation, and chronic hemorrhoidal disease.
Physical Findings and Clinical Presentation
Pain with defecation is the most common presenting symptom. Patients may also report rectal bleeding, narrowing of stools, severe constipation, outlet obstruction, fecal incontinence, tenesmus, or urgency. A careful history should assess prior anorectal surgery, Crohn disease, radiation exposure, or perianal trauma. On physical examination, visual inspection may reveal skin tags or chronic fissures. Digital rectal examination typically demonstrates a narrowed anal canal with difficulty passing a lubricated finger. In severe cases, examination under anesthesia may be required to adequately assess the stricture.
Etiology
Anorectal strictures are broadly divided into congenital, primary, and secondary causes. Congenital strictures are pediatric conditions related to abnormal embryologic development, including anal atresia and imperforate anus. Primary strictures usually occur in elderly patients due to fibrous involution of perianal tissues. Secondary strictures are the most common and are typically iatrogenic, most often following hemorrhoidectomy or other anorectal surgeries such as low anterior resection, ileal pouch–anal anastomosis, anopexy, or excision of perianal skin lesions. Other secondary causes include fibrosis of the anoderm or distal rectal mucosa, anal canal muscle hypertrophy or spasm, neoplastic conditions (such as Bowen disease, Paget disease, anal squamous cell carcinoma, rectal adenocarcinoma, or condyloma acuminata), inflammatory diseases (including anal fissure, Crohn disease, tuberculosis, actinomycosis, lymphogranuloma venereum, and chronic suppuration), traumatic causes (radiation therapy, perineal burns, hot water enemas, ibuprofen suppositories, and chronic laxative abuse), and sexually transmitted infections.
Diagnosis and Differential Diagnosis
Anorectal stricture is primarily a clinical diagnosis. The differential diagnosis includes anorectal or rectal neoplasm, inflammatory bowel disease, and traumatic injury. Any suspicious lesions identified during examination should be biopsied to exclude malignancy or inflammatory pathology.
Workup
Although the diagnosis is clinical, evaluation should ensure that secondary causes such as neoplasm or inflammatory disease are excluded. Regardless of etiology, hydration, fiber supplementation, and stool softeners should be initiated in all patients to reduce symptoms and prevent further injury.
Treatment
Management depends on severity and underlying cause. Nonpharmacologic therapy includes manual dilation using digital techniques or commercial dilators, which may be initiated in the clinic or operating room and continued on an outpatient basis for mild to moderate strictures. Surgical options include resection of neoplasm, stricturoplasty, or anoplasty. While multiple operative techniques have been described, there is no consensus on a single superior approach; all aim to replace scar tissue with healthy, pliable anoderm within the anal canal.
Chronic Management
For mild disease, conservative measures such as stool softeners, fiber supplementation, adequate hydration, and dietary modification may be sufficient to control symptoms without the need for procedural intervention.
Prevention and Complementary Considerations
The most effective management of postsurgical anorectal stricture is prevention. Proper surgical technique during anorectal procedures, including preservation of anoderm and, in some cases, internal sphincterotomy, can significantly reduce the risk of developing stenosis.
Disposition and Referral
Mild strictures can usually be managed on an outpatient basis. Moderate to severe strictures require evaluation by a colorectal surgeon. Referral is also indicated when there is concern for neoplasm, failure of conservative management, or inability of the clinician to pass a lubricated finger into the rectum during examination.
Basic Information and Definition
An anorectal stricture, also referred to as anal stenosis, is an abnormal narrowing of the anal canal. Strictures are classified according to both severity and location. Severity ranges from mild, in which a well-lubricated finger or medium Hill-Ferguson retractor can pass easily, to moderate, where passage is possible only with forceful dilation, and severe, where no passage is possible. Location is described as low (at least 0.5 cm distal to the dentate line), middle (within 0.5 cm on either side of the dentate line), or high (at least 0.5 cm proximal to the dentate line).
Synonyms and Coding
Anorectal stricture is also known as anal stenosis or Küss disease. The ICD-10-CM code used is K62.4, which denotes stenosis of the anus and rectum.
Epidemiology and Risk Factors
Hemorrhoid surgery is the most common overall cause of anorectal stricture, occurring in approximately 5% to 10% of patients after radical hemorrhoidectomy, particularly for grade III and IV hemorrhoidal disease. The risk of developing a stricture is directly related to the extent of anoderm resection. Other important risk factors include prior anorectal surgery, inflammatory bowel disease, previous pelvic radiation, and chronic hemorrhoidal disease.
Physical Findings and Clinical Presentation
Pain with defecation is the most common presenting symptom. Patients may also report rectal bleeding, narrowing of stools, severe constipation, outlet obstruction, fecal incontinence, tenesmus, or urgency. A careful history should assess prior anorectal surgery, Crohn disease, radiation exposure, or perianal trauma. On physical examination, visual inspection may reveal skin tags or chronic fissures. Digital rectal examination typically demonstrates a narrowed anal canal with difficulty passing a lubricated finger. In severe cases, examination under anesthesia may be required to adequately assess the stricture.
Etiology
Anorectal strictures are broadly divided into congenital, primary, and secondary causes. Congenital strictures are pediatric conditions related to abnormal embryologic development, including anal atresia and imperforate anus. Primary strictures usually occur in elderly patients due to fibrous involution of perianal tissues. Secondary strictures are the most common and are typically iatrogenic, most often following hemorrhoidectomy or other anorectal surgeries such as low anterior resection, ileal pouch–anal anastomosis, anopexy, or excision of perianal skin lesions. Other secondary causes include fibrosis of the anoderm or distal rectal mucosa, anal canal muscle hypertrophy or spasm, neoplastic conditions (such as Bowen disease, Paget disease, anal squamous cell carcinoma, rectal adenocarcinoma, or condyloma acuminata), inflammatory diseases (including anal fissure, Crohn disease, tuberculosis, actinomycosis, lymphogranuloma venereum, and chronic suppuration), traumatic causes (radiation therapy, perineal burns, hot water enemas, ibuprofen suppositories, and chronic laxative abuse), and sexually transmitted infections.
Diagnosis and Differential Diagnosis
Anorectal stricture is primarily a clinical diagnosis. The differential diagnosis includes anorectal or rectal neoplasm, inflammatory bowel disease, and traumatic injury. Any suspicious lesions identified during examination should be biopsied to exclude malignancy or inflammatory pathology.
Workup
Although the diagnosis is clinical, evaluation should ensure that secondary causes such as neoplasm or inflammatory disease are excluded. Regardless of etiology, hydration, fiber supplementation, and stool softeners should be initiated in all patients to reduce symptoms and prevent further injury.
Treatment
Management depends on severity and underlying cause. Nonpharmacologic therapy includes manual dilation using digital techniques or commercial dilators, which may be initiated in the clinic or operating room and continued on an outpatient basis for mild to moderate strictures. Surgical options include resection of neoplasm, stricturoplasty, or anoplasty. While multiple operative techniques have been described, there is no consensus on a single superior approach; all aim to replace scar tissue with healthy, pliable anoderm within the anal canal.
Chronic Management
For mild disease, conservative measures such as stool softeners, fiber supplementation, adequate hydration, and dietary modification may be sufficient to control symptoms without the need for procedural intervention.
Prevention and Complementary Considerations
The most effective management of postsurgical anorectal stricture is prevention. Proper surgical technique during anorectal procedures, including preservation of anoderm and, in some cases, internal sphincterotomy, can significantly reduce the risk of developing stenosis.
Disposition and Referral
Mild strictures can usually be managed on an outpatient basis. Moderate to severe strictures require evaluation by a colorectal surgeon. Referral is also indicated when there is concern for neoplasm, failure of conservative management, or inability of the clinician to pass a lubricated finger into the rectum during examination.
- Published on
KembaraXtra-Medicine- Anorexia Nervosa
Basic Information and Definition
Anorexia nervosa is a serious psychiatric disorder characterized by abnormal eating behaviors, intense fear of weight gain, severe self-induced weight loss, and a distinct disturbance in body image and self-perception. The disorder involves both psychological and physiological components and can affect nearly every organ system. It is classified into restricting type and binge-eating/purging type. ICD-10-CM codes include F50.00 (unspecified), F50.01 (restricting type), and F50.02 (binge-eating/purging type).
Epidemiology and Demographics
In the United States, anorexia nervosa affects approximately 0.2% to 1.3% of the general population, with an annual incidence of 5 to 10 cases per 100,000 individuals. The disorder is strongly associated with activities that emphasize thinness, such as competitive athletics and modeling. Females are disproportionately affected, with a female-to-male ratio of approximately 20:1. About 0.5% to 1% of women aged 15 to 30 years and up to 1.5% of teenage girls are affected. Adolescence to young adulthood is the most common age of onset, with a mean onset around 17 years.
Physical Findings and Clinical Presentation
Eating disorders can present with subtle, nonspecific symptoms in early or mild cases, including fatigue, cold intolerance, dizziness, and low energy, making early recognition challenging. Children and adolescents are particularly vulnerable due to ongoing growth and development. In moderate to severe anorexia nervosa, patients often appear markedly emaciated and may wear layered clothing to conceal weight loss. The skin is typically dry, may exhibit lanugo hair, and can appear yellowish due to carotenodermia. Hair thinning, brittle nails, bradycardia, hypotension, hypothermia, and bradypnea are common. Peripheral edema may occur. In females, normal fat distribution is lost, although axillary and pubic hair are usually preserved.
Etiology and Pathophysiology
The etiology of anorexia nervosa is multifactorial and incompletely understood, involving sociocultural pressures, psychological vulnerabilities, familial dynamics, and genetic predisposition. A history of sexual abuse has been reported in up to half of affected individuals. Psychologically, patients often struggle with low self-esteem, impaired identity formation, and a strong need for control. Body weight and food intake may become central mechanisms through which individuals attempt to exert control over their environment and emotions.
Diagnostic Criteria
Diagnosis is based on clinical assessment and DSM-5 criteria. These include restriction of energy intake leading to significantly low body weight for age, sex, and developmental stage; intense fear of gaining weight or persistent behavior interfering with weight gain; and disturbance in body image or lack of recognition of the seriousness of low body weight. Subtypes include the restricting type, characterized by dieting, fasting, or excessive exercise without bingeing or purging, and the binge-eating/purging type, which includes recurrent binge eating or purging behaviors. Amenorrhea, although historically emphasized, may be absent in younger adolescents and is no longer required for diagnosis.
Differential Diagnosis
Conditions that may mimic or coexist with anorexia nervosa include other eating disorders such as bulimia nervosa and binge eating disorder, substance use disorders, major depressive disorder, obsessive-compulsive disorder, schizophrenia, and conversion disorder. Medical causes of weight loss must also be considered, including malignancy, endocrine disorders (such as Addison disease, diabetes mellitus, thyroid disorders, or panhypopituitarism), gastrointestinal diseases (celiac disease, Crohn disease, parasitic infections), and chronic infections such as tuberculosis or HIV.
Workup and Screening
Screening for eating disorders should be incorporated into routine psychosocial assessments, especially in adolescents. Patients may minimize symptoms; therefore, collateral history from parents or caregivers is essential. The SCOFF questionnaire is a useful screening tool, with high sensitivity for anorexia and bulimia when two or more responses are positive. Baseline electrocardiography is recommended for all patients to assess for QT interval prolongation, which is associated with increased risk of sudden cardiac death. A dual-energy x-ray absorptiometry (DEXA) scan should be considered after six months of amenorrhea to evaluate for osteopenia or osteoporosis.
Laboratory Findings
Laboratory results may be normal in mild cases. Common abnormalities include endocrine changes such as decreased gonadotropins, estrogens, and thyroid hormones, with normal thyroid-stimulating hormone and elevated cortisol. Hematologic abnormalities may include leukopenia, anemia, thrombocytopenia, and reduced inflammatory markers. Electrolyte disturbances such as hypokalemia, hypomagnesemia, hypocalcemia, hypophosphatemia, metabolic alkalosis, and hypercholesterolemia may occur. Elevated plasma beta-carotene levels can help distinguish anorexia nervosa from other causes of starvation.
Treatment and Nonpharmacologic Management
Management requires a multidisciplinary approach involving medical, nutritional, and psychological care. A target weight should be established, aiming for 100% of ideal body weight in adolescents and 90% to 100% in adults. Weight restoration should proceed gradually, with initial caloric intake of 800 to 1200 kcal per day in small, frequent meals, advancing to 1500 to 3000 kcal as tolerated. Electrolytes must be monitored closely to prevent refeeding syndrome. In severe cases, enteral or parenteral nutrition may be necessary. Mealtimes should emphasize support rather than confrontation, and post-meal supervision may be required to prevent purging or excessive exercise.
Acute Management and Severity Assessment
Severity is categorized by body mass index in adults or BMI percentile in children and adolescents. Mild disease corresponds to a BMI of 17 kg/m² or higher, moderate disease to BMI 16–16.99, severe disease to BMI 15–15.99, and extreme disease to BMI below 15. Most patients can be managed as outpatients; however, inpatient care is indicated for medical instability, severe electrolyte disturbances, significant bradycardia or hypotension, prolonged QT interval, rapid weight loss, failure of outpatient treatment, or suicidal ideation. Pharmacologic therapy generally has limited benefit unless comorbid depression, anxiety, or obsessive-compulsive symptoms are present.
Chronic Management and Psychotherapy
Long-term psychotherapy is central to recovery and may need to continue for years. Treatment focuses on body image, self-esteem, interpersonal relationships, and relapse prevention. Family-based therapy is particularly effective in children and adolescents and is strongly recommended.
Disposition and Prognosis
The long-term prognosis of anorexia nervosa is guarded, with many patients experiencing relapses or persistent disordered eating and body image distortion. Menstrual function typically returns within six months of achieving 90% of ideal body weight, although pregnancy can occur even in the presence of amenorrhea. Mortality rates range from 5% to 20%, significantly higher than in age-matched peers, with common causes including electrolyte imbalance, starvation, and suicide. Favorable prognostic factors include early diagnosis, prompt treatment initiation, strong family support, and positive therapeutic relationships.
Referral and Indications for Hospitalization
Hospitalization should be considered for severe dehydration, electrolyte abnormalities, cardiac arrhythmias, significant physiologic instability, intractable purging, suicidal thoughts, weight loss exceeding 30% of ideal body weight, rapid ongoing weight loss, or failure of outpatient nutritional rehabilitation. Early involvement of mental health specialists is essential to optimize outcomes.
Basic Information and Definition
Anorexia nervosa is a serious psychiatric disorder characterized by abnormal eating behaviors, intense fear of weight gain, severe self-induced weight loss, and a distinct disturbance in body image and self-perception. The disorder involves both psychological and physiological components and can affect nearly every organ system. It is classified into restricting type and binge-eating/purging type. ICD-10-CM codes include F50.00 (unspecified), F50.01 (restricting type), and F50.02 (binge-eating/purging type).
Epidemiology and Demographics
In the United States, anorexia nervosa affects approximately 0.2% to 1.3% of the general population, with an annual incidence of 5 to 10 cases per 100,000 individuals. The disorder is strongly associated with activities that emphasize thinness, such as competitive athletics and modeling. Females are disproportionately affected, with a female-to-male ratio of approximately 20:1. About 0.5% to 1% of women aged 15 to 30 years and up to 1.5% of teenage girls are affected. Adolescence to young adulthood is the most common age of onset, with a mean onset around 17 years.
Physical Findings and Clinical Presentation
Eating disorders can present with subtle, nonspecific symptoms in early or mild cases, including fatigue, cold intolerance, dizziness, and low energy, making early recognition challenging. Children and adolescents are particularly vulnerable due to ongoing growth and development. In moderate to severe anorexia nervosa, patients often appear markedly emaciated and may wear layered clothing to conceal weight loss. The skin is typically dry, may exhibit lanugo hair, and can appear yellowish due to carotenodermia. Hair thinning, brittle nails, bradycardia, hypotension, hypothermia, and bradypnea are common. Peripheral edema may occur. In females, normal fat distribution is lost, although axillary and pubic hair are usually preserved.
Etiology and Pathophysiology
The etiology of anorexia nervosa is multifactorial and incompletely understood, involving sociocultural pressures, psychological vulnerabilities, familial dynamics, and genetic predisposition. A history of sexual abuse has been reported in up to half of affected individuals. Psychologically, patients often struggle with low self-esteem, impaired identity formation, and a strong need for control. Body weight and food intake may become central mechanisms through which individuals attempt to exert control over their environment and emotions.
Diagnostic Criteria
Diagnosis is based on clinical assessment and DSM-5 criteria. These include restriction of energy intake leading to significantly low body weight for age, sex, and developmental stage; intense fear of gaining weight or persistent behavior interfering with weight gain; and disturbance in body image or lack of recognition of the seriousness of low body weight. Subtypes include the restricting type, characterized by dieting, fasting, or excessive exercise without bingeing or purging, and the binge-eating/purging type, which includes recurrent binge eating or purging behaviors. Amenorrhea, although historically emphasized, may be absent in younger adolescents and is no longer required for diagnosis.
Differential Diagnosis
Conditions that may mimic or coexist with anorexia nervosa include other eating disorders such as bulimia nervosa and binge eating disorder, substance use disorders, major depressive disorder, obsessive-compulsive disorder, schizophrenia, and conversion disorder. Medical causes of weight loss must also be considered, including malignancy, endocrine disorders (such as Addison disease, diabetes mellitus, thyroid disorders, or panhypopituitarism), gastrointestinal diseases (celiac disease, Crohn disease, parasitic infections), and chronic infections such as tuberculosis or HIV.
Workup and Screening
Screening for eating disorders should be incorporated into routine psychosocial assessments, especially in adolescents. Patients may minimize symptoms; therefore, collateral history from parents or caregivers is essential. The SCOFF questionnaire is a useful screening tool, with high sensitivity for anorexia and bulimia when two or more responses are positive. Baseline electrocardiography is recommended for all patients to assess for QT interval prolongation, which is associated with increased risk of sudden cardiac death. A dual-energy x-ray absorptiometry (DEXA) scan should be considered after six months of amenorrhea to evaluate for osteopenia or osteoporosis.
Laboratory Findings
Laboratory results may be normal in mild cases. Common abnormalities include endocrine changes such as decreased gonadotropins, estrogens, and thyroid hormones, with normal thyroid-stimulating hormone and elevated cortisol. Hematologic abnormalities may include leukopenia, anemia, thrombocytopenia, and reduced inflammatory markers. Electrolyte disturbances such as hypokalemia, hypomagnesemia, hypocalcemia, hypophosphatemia, metabolic alkalosis, and hypercholesterolemia may occur. Elevated plasma beta-carotene levels can help distinguish anorexia nervosa from other causes of starvation.
Treatment and Nonpharmacologic Management
Management requires a multidisciplinary approach involving medical, nutritional, and psychological care. A target weight should be established, aiming for 100% of ideal body weight in adolescents and 90% to 100% in adults. Weight restoration should proceed gradually, with initial caloric intake of 800 to 1200 kcal per day in small, frequent meals, advancing to 1500 to 3000 kcal as tolerated. Electrolytes must be monitored closely to prevent refeeding syndrome. In severe cases, enteral or parenteral nutrition may be necessary. Mealtimes should emphasize support rather than confrontation, and post-meal supervision may be required to prevent purging or excessive exercise.
Acute Management and Severity Assessment
Severity is categorized by body mass index in adults or BMI percentile in children and adolescents. Mild disease corresponds to a BMI of 17 kg/m² or higher, moderate disease to BMI 16–16.99, severe disease to BMI 15–15.99, and extreme disease to BMI below 15. Most patients can be managed as outpatients; however, inpatient care is indicated for medical instability, severe electrolyte disturbances, significant bradycardia or hypotension, prolonged QT interval, rapid weight loss, failure of outpatient treatment, or suicidal ideation. Pharmacologic therapy generally has limited benefit unless comorbid depression, anxiety, or obsessive-compulsive symptoms are present.
Chronic Management and Psychotherapy
Long-term psychotherapy is central to recovery and may need to continue for years. Treatment focuses on body image, self-esteem, interpersonal relationships, and relapse prevention. Family-based therapy is particularly effective in children and adolescents and is strongly recommended.
Disposition and Prognosis
The long-term prognosis of anorexia nervosa is guarded, with many patients experiencing relapses or persistent disordered eating and body image distortion. Menstrual function typically returns within six months of achieving 90% of ideal body weight, although pregnancy can occur even in the presence of amenorrhea. Mortality rates range from 5% to 20%, significantly higher than in age-matched peers, with common causes including electrolyte imbalance, starvation, and suicide. Favorable prognostic factors include early diagnosis, prompt treatment initiation, strong family support, and positive therapeutic relationships.
Referral and Indications for Hospitalization
Hospitalization should be considered for severe dehydration, electrolyte abnormalities, cardiac arrhythmias, significant physiologic instability, intractable purging, suicidal thoughts, weight loss exceeding 30% of ideal body weight, rapid ongoing weight loss, or failure of outpatient nutritional rehabilitation. Early involvement of mental health specialists is essential to optimize outcomes.
