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Introduction
1. Anatomy
2. Microbiology
3. Physiology
4. Pathology
4.1 General pathology
4.2 Central and peripheral nervous system
4.3 Cardiovascular system
4.4 Respiratory system
4.5 Hematology and oncology
4.6 Gastrointestinal pathology
4.7 Renal, endocrine and reproductive system
4.8 Musculoskeletal system
4.8.1 Infectious disorders
4.8.2 Inflammatory and degenerative disorders of bone
4.8.3 Metabolic disorders of bone
4.8.4 Pediatric disorders
4.8.5 Miscellaneous disorders
5. Pharmacology
6. Immunology
7. Biochemistry
8. Cell and molecular biology
9. Biostatistics and epidemiology
10. Genetics
11. Behavioral science
Wrapping up
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4.8.5 Miscellaneous disorders
Achievable USMLE/1
4. Pathology
4.8. Musculoskeletal system

Miscellaneous disorders

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Dupuytren contracture

Dupuytren contracture is a proliferative disorder that causes thickening and contracture of the palmar fascia. It’s seen more commonly in males older than 50 years of Northern European descent. It’s inherited as an autosomal dominant disease.

Risk factors include alcohol, smoking, trauma, anti-epileptic medications, and diabetes mellitus. Cytokine-mediated proliferation of myofibroblasts occurs, along with excessive deposition of type III and type I collagen.

It typically develops over years, starting as painful lumps, nodules, and cords in the palm. Over time, this can lead to contractures involving one or more fingers. Some patients may also develop thickened tissue on the feet (Ledderhose disease) or penis (Peyronie’s disease).

Treatment includes physical therapy, corticosteroid injection into painful nodules, injection of Cl.histolyticum collagenase, and fasciectomy.

Rhabdomyolysis

Rhabdomyolysis is characterized by skeletal muscle damage that releases excessive amounts of intracellular myoglobin into the circulation. Myoglobin can then settle in the renal tubules, leading to acute renal failure. Renal injury also occurs due to vasoconstriction and free radical damage.

Common causes of rhabdomyolysis include severe trauma (e.g., crush injuries), lightning strikes, burns, heat stroke, viral infections (e.g., Influenza, HIV, EBV), bacterial infections (e.g., Legionella), falciparum malaria, McArdle disease, carnitine deficiency, electrolyte imbalances, reduced ATP, drugs (e.g., statins, fibrates), alcohol, and snake venom.

Symptoms include muscle cramping, myalgia, dark urine, and fatigue. Complications include hyperkalemia, hypo and hypercalcemia, hyperuricemia, compartment syndrome, DIC, arrhythmias, and renal failure.

Plasma creatine kinase is elevated, myoglobin is present in urine, and the urine dipstick test is positive for blood.

Management includes hydration, correction of electrolyte imbalances, and treatment of complications and underlying conditions. Alkalinization of urine with sodium bicarbonate helps prevent renal failure.

Fibromyalgia

Fibromyalgia is a chronic musculoskeletal pain syndrome. It isn’t inflammatory or autoimmune in nature, but it’s associated with abnormal central pain processing in the brain. It’s more common in women.

Symptoms include multifocal pain and tenderness, fatigue, brain fog, joint stiffness, headache, and poor sleep. It’s often associated with irritable bowel syndrome.

Fibromyalgia is a clinical diagnosis of exclusion, since lab work (including ESR) is normal. Management includes pain medications, steroids, duloxetine, and tricyclic antidepressants.

Polymyalgia rheumatica

Polymyalgia rheumatica is an inflammatory disorder (vasculitis) seen in women over the age of 50 years. It’s characterized by muscle pain and stiffness in the shoulder, hip, and neck area. It’s often associated with giant cell or temporal arteritis.

Pain and stiffness are usually worse upon waking in the morning or after resting, and they typically last an hour or more. Joint pain and swelling may be present. Weight loss and flu-like symptoms may also be seen.

ESR and CRP are elevated, while creatine kinase is normal. The cytokine IL 6 is high.

Treatment is with corticosteroids, IL 6 inhibitors like sarilumab and tocilizumab, methotrexate, TNF alpha inhibitors like infliximab, and analgesics.

Polymyositis Dermatomyositis
  • Inflammatory myopathy with progressive, symmetric, predominantly proximal muscle weakness
  • Elevated creatine kinase
  • Autoantibodies
  • Inflammatory infiltrates on muscle biopsy
  • Chronic muscle weakness, fatigue
  • Rare in childhood
  • CD8+ mediated damage of MHC I expressing muscle fibers
  • Extraocular muscles are spared, no ptosis
  • Involvement of heart, lungs, gastrointestinal tract, kidney, increased risk of malignancies
  • Perivascular inflammation in the endomysium
  • Inflammatory myopathy with progressive, symmetric, predominantly proximal muscle weakness
  • Elevated creatine kinase
  • Autoantibodies
  • Inflammatory infiltrates on muscle biopsy
  • Skin rash with chronic muscle weakness, fatigue; violaceous eruption on knuckles called Gottron’s papules, periorbital heliotrope rash with edema, erythematous rash on face, neck, hands, back
  • Affects all age groups
  • CD4+ mediated damage of vascular endothelium, complement activation
  • Extraocular muscles are spared, no ptosis
  • Involvement of heart, lungs, gastrointestinal tract, kidney, increased risk of malignancies
  • Perivascular inflammation in the interfascicular septae or periphery of fascicles

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