​Kembara Xtra - Medicine - Sarcoidosis

​Kembara Xtra - Medicine - Sarcoidosis 
Sarcoidosis is a multisystem, noninfectious, granulomatous disease that primarily affects young and middle-aged individuals.Frequently has lung infiltrates, eye or cutaneous lesions, as well as bilateral hilar adenopathy.
-Abnormal chest x-rays (CXRs) are used to diagnose it in about 50% of instances in people who have no symptoms. Any organ could be affected.
 Mainly the pulmonary system, but also the cardiovascular, gastrointestinal, hematologic, endocrine, renal, neurologic, dermatologic, ophthalmologic, and musculoskeletal systems are impacted.
Synonym(s): Besnier-Boeck disease; Boeck sarcoid; Scheuermann disease; Löfgren syndrome (erythema nodosum [EN], hilar adenopathy, fever, arthralgias); Heerfordt syndrome (uveitis, parotid hypertrophy, facial palsy, fever); 


Epidemiology 

Estimated incidence is 6 per 100 person-years.

Estimated prevalence of 10 to 20/100,000 people, with a female incidence rate of 11/100,000 per year. Usually affects younger people, with men and women experiencing the peak incidence between the ages of 40 and 59 and 50 to 69 respectively. Unusual in children

Pathophysiology and Etiology 
Despite intensive research, the cause is still unknown. The initial lung lesion is CD4+ T-cell alveolitis, which results in noncaseating granulomata and may go away or may undergo fibrosis. This lesion is thought to be caused by an excessive cell-mediated immune response to unknown antigen(s). "Immune paradox" occurs when other organs are anergic but the affected organs display a strong immune response.

Reports of familial clustering have been linked genetically to a region of the MHC on the short arm of chromosome 6.
Despite being widespread, it is more common in Scandinavians, Japanese, Black Americans, and women.
Between 5 to 40 cases per 100,000 people in Northern Europe. 35 instances per 100,000 Black Americans, compared to 11 cases per 100,000 Caucasian Americans

Risk Elements 

The exact pathogenesis and etiology are yet unknown.


Diagnosis 
All individuals with probable sarcoidosis should have a thorough examination.

Patients may not have any symptoms in the past.
Patients may complain in general terms about the following:
- An ineffective cough or breathlessness - A fever or nocturnal sweats
- Losing weight
- General weariness
- Headaches - Palpitations - Eye pain
Skin lesions, polyarthritis, encephalopathy, seizures, and (rarely) hydrocephalus
- Systemic symptoms are more common in patients over 70 years old.

Clinical evaluation 
The majority of patients get a routine physical examination. The lungs may show wheezing or tiny interstitial crackles.
30% of patients experience extrapulmonary symptoms, which may include:
- Uveitis or further eye conditions: cataracts, glaucoma, papilledema, lacrimal gland hypertrophy, conjunctival nodules,
- Palsies of the cranial nerve
- Arrhythmias - Hepatosplenomegaly - Polyarthritis - Rashes - Salivary gland edema or lymphadenopathy - Maculopapular of nares, eyelids, forehead, base of neck near hairline, and past trauma sites
Plaques (lupus pernio) on the nose, cheeks, chin, and ears; waxy nodular of the face, trunk, and extensor surfaces of the extremities
EN (a part of the Löfgren syndrome)

 Differential diagnosis 
Infectious granulomatous conditions like TB and fungi
 Pneumonitis with hypersensitivity, lymphoma, or other cancers
The erylliosis

Laboratory Results 

There is no conclusive test for diagnosis, although the following factors point to one:
 Radiographic and clinical symptoms
 -excluding alternate diagnosis.
Identification of noncaseating granulomas by histopathology


Initial examinations (lab, imaging)

Hypergammaglobulinemia, eosinophilia, and leukopenia on the CBC
. Hepatic involvement with abnormal liver function and elevated alkaline phosphatase.
Up to 10% of patients experience hypercalciuria; hypercalcemia is less common.
Serum ACE is high in more than 75% of cases, however it's neither diagnostic nor disqualifying
- Drug use can affect test results: Prednisone will normalize the gallium scan and reduce serum ACE. ACE inhibitors reduce the level of ACE in the serum.
- Lab results may be affected by disorders: Diabetes, TB, hyperthyroidism, and various malignancies can also raise the serum ACE level.
Granulomas and hilar adenopathy may be seen on a CXR or CT scan.
Using Scadding classification, CXRs are staged.
Normal is stage 0, bilateral hilar adenopathy is stage 1, and parenchymal infiltrates, mainly in the upper lobes, are stage 2.
Parenchymal infiltrates with diminishing hilar adenopathy characterize stage 3.
- Stage 4: Volume reduction, bronchiectasis, calcification, or cyst formation in parenchymal infiltrates
.
Peribronchial illness may be discovered by high-resolution chest CT scan.
Cardiac PET scan may reveal cardiac sarcoidosis. Positron emission tomography (PET) scan can show areas of disease activity in the lungs, lymph nodes, and other places of the body. However, PET scan cannot distinguish between malignancy and sarcoidosis.
Despite the fact that serum amyloid A and adenosine deaminase levels are raised in sarcoidosis, these tests are not employed in clinical settings because of their poor sensitivity and specificity.

Other/Diagnostic Procedures

PFTs for pulmonary function may show a restrictive pattern with lower DLCO for carbon monoxide diffusing capacity.
Bronchoalveolar lavage fluid has a higher CD4-to-CD8 ratio when a disease is active. ongoing investigation on whether D-dimer levels in BAL contribute to the diagnosis of sarcoidosis.
The results of an ophthalmologic examination may show conjunctivitis, uveitis, or retinal vasculitis.
Tuberculin skin test, ECG,
In the event that the lungs are afflicted, bronchoscopy with biopsy of the central and peripheral airways is beneficial. Biopsy of the lesions should demonstrate noncaseating granulomas. The diagnostic yield of transbronchial needle aspiration guided by endobronchial US (EBUS) may be higher.
Kveim test (ongoing research): To elicit a sarcoid granulomatous response over three weeks, similar to a tuberculin skin test, sterilized splenic cells from a patient with sarcoidosis are injected into an intradermal skin test.

Alert 

It is not required to do a biopsy if symptoms suggest Löfgren syndrome (acute sarcoid with bilateral hilar lymphadenopathy, EN, and generalized arthritis/arthralgias), as the prognosis is good with observation alone, and a biopsy would not modify care.


Noncaseating epithelioid granulomas without signs of mycobacterial or fungi infection, according to the test interpretation

Management 

No treatment may be necessary in those who are asymptomatic, but it may be necessary if the patient has cardiac, CNS, renal, or ophthalmic involvement. Many people experience spontaneous remission.
No therapy is recommended but frequent follow-up is advised for asymptomatic patients with stage I to stage III radiographic abnormalities and normal or somewhat impaired lung function.
The premise for treating pulmonary symptoms is impairment.
- Decreasing lung function and pulmonary symptoms, as well as deteriorating radiographic findings

Medication 
Hypercalcemia and diseases of the heart, brain, or eyes are suggested for systemic therapy. As many pulmonary sarcoidosis patients are asymptomatic or experience a spontaneous remission, the majority of patients do not need pharmacological treatment.

Initial Line

 Systemic corticosteroids in symptomatic individuals or with deteriorating lung function or radiographic abnormalities; no FDA-approved treatment for sarcoidosis.
- There is no established ideal glucocorticoid dosage. Tuberculosis must be ruled out before starting glucocorticoids.
- Typically prednisone, 0.3 to 0.6 mg/kg ideal body weight (20 to 40 mg/day) for 4 to 6 weeks - if stable, taper by 5 mg/week to 10 to 20 mg/day during the following 6 weeks.
- 10 to 20 mg per day for 8 to 12 months if there is no relapse.
Relapse is typical.
- Patients with acute respiratory failure, cardiac, neurologic, or ophthalmic illness may require higher doses (80 to 100 mg/day).
Topical steroids may be useful in people with skin conditions.
In cases with early illness and moderate pulmonary symptoms, inhaled steroids (budesonide 800 to 1,600 mg BID) may be of some therapeutic benefit.
- Restrictions and important potential interactions:
Consult the medication profiles provided by the manufacturers.


Next Line
All glucocorticoid substitutes have a significant risk of severe side effects, including myelosuppression, hepatotoxicity, and opportunistic infection. Examine for steroid compliance, concomitant disease, or other complicating reasons causing steroid failure before using these drugs. It is advised to refer patients to specialists.
Methotrexate: start with 7.5 mg/week and work your way up to 10 to 15 mg/week. not to be used in cases of liver disease
Azathioprine is typically taken in addition to prednisone in an effort to reduce steroid dosages.
Use of immunosuppressants like methotrexate or azathioprine will necessitate routine CBC and LFT monitoring.
Antimalarial drugs like chloroquine and hydroxychloroquine have undergone clinical trials without clearly showing any benefits.
In circumstances where other treatments have failed, tumor necrosis factor antagonists like infliximab have been helpful.


Referral 
If additional organ systems are involved, a pulmonologist may follow, with referrals to other specialists as necessary; if second-line therapy is required, a specialist should follow.

Surgical Techniques 

In severe, refractory cases, lung transplantation may be necessary; long-term effects remain unknown.

Take Action 

There is a lack of information regarding the best frequency for monitoring disease activity and the indications for particular testing.
Followed by suggestions.


Patient observation

Prednisone users should be checked every one to two months while taking their medication.
For the first two years after diagnosis, patients who do not need therapy should be examined every three months. During this time, a history and physical examination, as well as laboratory tests specific to the locations of disease activity, PFTs, and ambulatory pulse oximetry, should be performed.
If the disease is active, get an eye exam every six to twelve months if you're taking hydroxychloroquine.
- CBC, creatinine, calcium, LFTs, ECG, 25-hydroxy and 1,25-dihydroxyvitamin D, CXR, and ophthalmologic examination every year
 Additional tests based on the symptoms of each patient, such as a brain MRI, HRCT, echocardiography, Holter monitoring, urinalysis (UA), thyroid-stimulating hormone (TSH), and bone density
Some doctors utilize the serum ACE level to monitor the progression of the illness. When receiving treatment or when the condition is treated, ACE levels in people who had initially increased levels should return to normal.
If the illness is dormant, a history and physical examination, PFTs, ambulatory pulse oximetry, CBC, creatinine, calcium, liver enzymes, 1,25-dihydroxyvitamin D, ECG, and ophthalmologic exam should be performed annually.


Prognosis: Within two years, 50% of patients will experience spontaneous resolution.
After two years, 25% of patients will have considerable fibrosis but no further progression of the illness.
25% of patients will have a chronic illness (the percentage is higher in specific demographics, particularly Black Americans).
Patients who have used corticosteroids for longer than six months are more likely to develop chronic conditions.
5% is the overall death rate.

Patient complications such cor pulmonale and severe respiratory involvement are possible. Aspergillosis infection in the injured lung may cause pulmonary bleeding.
 Other organs, particularly the heart (congestive heart failure, arrhythmias), eyes (rarely blindness), and CNS, might be affected and suffer severe repercussions.

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