​Kembara Xtra - Medicine - Polymyositis / Dermatomyositis

​Kembara Xtra - Medicine - Polymyositis / Dermatomyositis 
Systemic connective tissue disease, occasionally accompanied by a distinctive skin rash, is characterized by inflammatory and degenerative alterations in the proximal muscles. Dermatomyositis is defined as the presence of skin manifestations, such as the Gottron sign (symmetric, scaly, violaceous, erythematous eruption over the extensor surfaces of the metacarpophalangeal and interphalangeal joints of the fingers) and heliotrope (reddish, violaceous eruption on the upper eyelids). The following are examples of various myositis conditions: Polymyositis/dermatomyositis as an overlap (often with lupus or systemic sclerosis or as part of mixed connective-tissue disease) Idiopathic polymyositis Idiopathic dermatomyositis Myositis connected to malignancy
 Necrotizing autoimmune myositis, frequently linked to statin use
 Inclusion body myositis (IBM), a subtype with unusual weakening patterns and biopsy results Cardiovascular, musculoskeletal, pulmonary, skin/exocrine, and other systems are impacted. Synonyms include myositis, inflammatory myopathy, and antisynthetase syndrome (subset with specific antibodies).

Epidemiology Incidence: Predominant ages: 5 to 15 years, 40 to 60 years, peak incidence in the mid-40s; Predominant sex: female > male (2:1); Estimated incidence: 1.2 to 19 per million population per year 2.4 to 33.8 patients per 100,000 people is the prevalence
Aspects of Geriatrics
Myositis or dermatomyositis in elderly persons increases the risk of developing cancer.
Child Safety Considerations
It's likely that childhood dermatomyositis is a distinct condition linked to muscle calcifications and cutaneous vasculitis.

Pathophysiology and Etiology 

Degenerative pathways may be significant in individuals with IBM. Inflammatory process, mediated by T cells and cytokine release, leading to damage to muscle cells (mostly skeletal muscles).
Unknown; possible viral and genetic influences 

genetics Weak associations with HLA-DR3, HLA-DRw52, and other human leukocyte antigens

Risk Elements 
family history of vasculitis or an autoimmune condition such systemic lupus or myositis

Vasculitis, Systemic lupus erythematosus (SLE), Mixed connective tissue disease, Progressive systemic sclerosis, malignancy more common in dermatomyositis

Diagnosis: Joint pain/swelling; dysphagia; dyspnea; rash on face, eyelids, hands, and arms; symmetric proximal muscular weakness causing difficulties rising from sitting or reclining positions; climbing stairs; raising arms

clinical assessment 

weak proximal muscles
Shoulder musculature
 Muscle swelliness, stiffness, or induration; Hip girdle muscles (difficulty standing from a seated or squatting position; weak hip flexors in the supine position) Distal muscular weakness is exclusively observed in IBM patients.
 Rash on the hands, fingers, upper chest, dorsal hands (particularly knuckle pads), and eyelids (also known as "mechanic's hands"). Periorbital swelling
Calcinosis cutis (cases in children) Mesenteric arterial insufficiency or infarction (in cases involving children) Cardiac dysfunction, arrhythmia, and failure


Differential diagnosis: Vasculitis; Amyotrophic lateral sclerosis; Sarcoidosis; Progressive systemic sclerosis; SLE; Rheumatoid arthritis; Muscular dystrophy; Lambert-Eaton syndrome; Rheumatoid arthritis; Endocrine disorders
- Cushing syndrome - Thyroid disease
 Drug-induced myopathies Infectious myositis (viral, bacterial, parasitic 
- Statins, Colchicine, and Corticosteroids are medications that decrease cholesterol.
- Sleep apnea syndrome - Alcohol - Chloroquine - Zidovudine - Electrolyte problems (magnesium, calcium, and potassium) - Heritable metabolic myopathies


Laboratory Results Four results are typically used to diagnose muscle component (myositis): - Weakness - Elevated aldolase and/or creatine kinase (CK) - Abnormal electromyogram (EMG) - Muscle biopsy results - Presence of a dermatomyositis-compatible skin rash - and a growing role for myositis-specific antibody (MSA) profiles. The proper workup for interstitial lung disease (ILD) and cancer can be guided by MSAs (2).


Initial examinations (lab, imaging)
Increased levels of CK, aldolase, serum AST, lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) Myoglobinuria, elevated ESR, rheumatoid factor positivity (50% of patients), positive antinuclear antibody (ANA) positivity (>50% of patients), and more. Anemia and leukocytosis are both present in 50% of individuals, respectively.
Anti-HMGCR (3-hydroxy-3-methylglutaryl-coenzyme A reductase) and anti-SRP antibodies are present in patients with necrotizing autoimmune myositis, and they are also seen in those with antisynthetase syndrome, which is linked to an increased incidence of ILD. Hyperglobulinemia (50% of patients).
Anti-U1 RNP, anti-PM-Scl, and anti-Ku antibodies observed in overlap myositis; Anti-MDA-5 antibody seen in overlap myositis with atypical rashes and severe ILD; Chest radiograph as part of first evaluation to screen for concomitant pulmonary disease or cancer

Tests in the Future & Special Considerations

 Improvement and deterioration are correlated with changes in muscle enzymes (CK or aldolase).
Some patients may benefit from an MRI to evaluate muscular edema and inflammation in order to choose the appropriate biopsy location or monitor their therapeutic response.

EMG: muscular irritability, low-amplitude potentials, polyphasic action potentials, and fibrillations  Muscle biopsy (quadriceps femoris or deltoid) Interpretation of the test Microscopic findings:
Degeneration of muscle fibers and phagocytosis of muscle waste
- Atrophy of the perifascicular muscle fibers
- Adult inflammatory cell infiltrates - Inclusion bodies observed by electron microscopy (IBM only)
Sarcoplasmic basophilia, enlarged muscle fibers, and vascular disease (dermatomyositis and infantile polymyositis)

Management 

Depending on the concerned speciality (dermatology, rheumatology, or neurology), the approach to treatment has varied, but there is a consensus statement accessible (3). The type of lesion, level of muscle involvement, existence of systemic symptoms, presence of MSAs, and patient age should all be taken into consideration when choosing a treatment plan.


First Line of Medicine

Prednisone, given at divided doses of 0.5 to 1.0 mg/kg every day,
- In acute and severe instances, an IV pulse dosage of methylprednisolone 1,000 mg per day for 3 to 5 days - Once the enzyme levels are normal, combine doses and gradually reduce the prednisone dosage.
- In most patients, maintenance doses of 5 to 10 mg/day are likely to be required.  Parallel steroid and immunosuppressive maintenance therapy is advised for the majority of patients: Patients with IBM have a very poor response to steroids and other first- and second-line medications in general. Examples of these medications include: - Azathioprine 1 mg/kg PO (arthritis dose) once daily or BID, - Methotrexate 10 to 25 mg po weekly, - Mycophenolate mofetil 2 to 3 mg daily, - Rash of dermatomyositis may require topical steroids or oral hydroxychloroquine.

Next Line
In cases where steroids are ineffective, other immunosuppressant medications, such as tacrolimus, chlorambucil, cyclosporin, and cyclophosphamide, may be given.
In refractory situations, adrenocorticotropic gel (ACTH gel) might be useful.
In refractory cases, a combination of methotrexate and azathioprine may be helpful.
In a small group of individuals with refractory illness, IVIG and rituximab have been shown to be beneficial. In patients with myositis who have autoantibodies present, particularly anti-Jo-1 and anti-Mi-2, rituxan may be more effective. In cases where steroids or other immunosuppressive medications are not appropriate, such as infections and tumors, IVIG can be a viable alternative.
Cyclophosphamide is often saved for serious conditions involving the heart or lungs.
Methotrexate should not be used in people with underlying renal illness, alcohol use disorders, past liver disease, pregnancy, or blood creatinine levels that are generally higher than 1.5 mg/dL.
 Safety measures
Prednisone: Adrenal suppression, salt and water retention, hypokalemia, osteoporosis, cataracts, and increased susceptibility to infection are among side effects of long-term steroid use.
- Azathioprine: Side effects include decreased bone marrow function, elevated liver function tests, and elevated infection risk.
- Methotrexate: Side effects with long-term use include stomatitis, bone marrow suppression, pneumonitis, and an increased risk of liver fibrosis and cirrhosis.


Referral Poor response to early steroid therapy Excessive steroid demand (unable to reduce prednisone to 20 mg/day after 4 to 6 months) Diagnostic ambiguity, typically due to increased muscle enzymes without typical symptoms or signs of muscle weakness

Surgical Techniques 

All that was indicated was the initial biopsy.

Alternative Therapies 

Physical therapy's advantages and disadvantages are not well established, particularly in cases of active muscular illness, while there is some evidence that it may be advantageous in cases of dormant disease. The quality of the research in this topic is poor.

Admission Inability to stand or walk Respiratory problems Fever or other infection-related symptoms Rarely required Inpatient evaluation 

Patient Follow-Up Monitoring
Follow muscular strength and functional ability coupled with muscle enzymes.
 Keep an eye out for side effects brought on by steroids, such as hypertension, hyperglycemia, and hypokalemia.
 Bone densitometry and evaluation of bisphosphonate, calcium, and vitamin D therapy  Appropriate laboratory testing, such as hematology, liver enzymes, and creatinine, should be carried out periodically if azathioprine, methotrexate, or another immunosuppressant is taken.
 As the patient responds to treatment, try to reduce or stop using the steroids.
Maintain immunosuppression for an extended period of time, taking into account the specifics of the patient, drug dangers, and relapse risk; time span is unspecified (months, years).


Diet 

Moderate calorie and sodium intake is necessary to prevent weight gain as a result of corticosteroid medication.


Patients should be educated to reduce excessive physical activity in the initial stages, when muscle enzyme levels are noticeably raised.
Make range-of-motion exercises a priority.
When muscle enzyme levels are stable, better, or normal, gradually introduce muscular strengthening.


The prognosis is 30% residual weakening.
20% have a chronic active illness.
 5-year survival is 65-75%, while mortality is 3- to 5-times higher than the average. The first year following diagnosis is when death increases the most.
Women, African Americans, people with dermatomyositis, IBM, or cancer have lower survival rates, and most patients get better with treatment.
ILD patients have a bad prognosis.
Most treatments have a dismal success rate with IBM patients.
20–50% have reached full recovery.


Pneumonia, infection, myocardial infarction, cancer (particularly breast and lung cancer), severe dysphagia, respiratory impairment brought on by muscle weakness and ILD, aspiration pneumonitis, steroid myopathy, and steroids-induced diabetes, hypertension, hypokalemia, and osteoporosis are all potential complications.

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