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X. Dolok, MD

Clinical Director, Stony Brook University School of Medicine

Most likely diagnosis: Dermatomyositis Next diagnostic step: Skeletal muscle biopsy Next step in therapy: Immunomodulatory therapy; cardiac and respiratory evaluation Analysis Objectives 1. Clinical Considerations the patient presented in this case has a subacute onset of proximal muscle pain and weakness, some swallowing (dysphagia) difficulties, and rash. Dermatomyositis differs from polymyositis by its immunopathogenesis but also by the involvement of skin, with rash, discoloration, and tissue calcification. Inclusion body myositis tends to present with a more gradual onset of weakness, which can date back several years by the time of diagnosis. Raynaud phenomenon: A condition resulting from poor circulation in the extremities. In a person with Raynaud phenomenon, when his or her skin is exposed to cold or the person becomes emotionally upset, the blood vessels under the skin spasm, and the blood flow slows. Clinical Approach Polymyositis and dermatomyositis are frequently considered together because they have similar clinical, laboratory, and pathologic features and because they progress at the same tempo. Although inclusion body myositis shares some features with polymyositis and dermatomyositis, it generally follows a more indolent course and is more refractory to therapy. Epidemiology and Clinical Features Dermatomyositis is more rare than polymyositis, affecting 10 people out of every 1 million. Although there is a juvenile form of this disease that begins between the ages of 5 and 15 years, it most commonly begins between the ages of 40 and 60 years. Dermatomyositis has a subacute (somewhat short and relatively severe) onset, usually worsening over a period of days or weeks, although it might also last for months. The distinguishing characteristic of dermatomyositis is a rash accompanying, or more often, preceding muscle weakness. The rash is described as patchy, bluish-purple discolorations on the face, neck, shoulders, upper chest, elbows, knees, knuckles, and back. Some patients might also develop hardened bumps of calcium deposits under the skin. In approximately one-fourth of adult cases, muscles ache and are tender to the touch. The disease has a more gradual onset compared to dermatomyositis and generally begins in the second decade of life. Approximately one-third of patients with polymyositis or dermatomyositis experience muscle tenderness and cramps. The chief clinical feature of polymyositis and dermatomyositis is progressive, painless symmetrical proximal muscle weakness, with symptoms possibly dating back to 3 to 6 months by the time of the diagnosis. Upper-extremity muscle weakness manifests as difficulty in performing activities that require holding the arms up, such as hair washing, shaving, or reaching into overhead cupboards. Neck muscle weakness may lead to difficulty raising the head from a pillow or even holding it up while standing. Involvement of pharyngeal muscles may result in hoarseness, dysphonia, dysphagia, and nasal regurgitation after swallowing. Lower-extremity proximal muscle weakness manifests as difficulty climbing stairs and rising from a seated or squatting position. Patients will often seek chairs with armrests to push off from or grab the sink or towel bar to rise from the toilet. Other Clinical Features Weakness is the major complaint, but proximal myalgias and constitutional symptoms such as fever, fatigue, and weight loss can occur. Interstitial pneumonitis occurs in approximately 10% of patients with polymyositis, usually developing gradually over the course of the illness. Electrocardiographic abnormalities are more common, with left anterior fascicular block and right bundle-branch block representing the most frequent conduction defects. Both polymyositis and dermatomyositis were associated with an increased risk of malignancy, with a threefold risk demonstrated in patients with dermatomyositis and a 1. The types of malignancy generally reflected those expected for age and sex although ovarian cancer was overrepresented in women with dermatomyositis, and both groups of patients displayed a greater-than- expected occurrence of nonHodgkin lymphoma.

Toxins and metabolic causes are important considerations but the history and initial laboratory studies are not suggestive. The presence of monoclonal gammopathy is concerning and warrants further workup as it may be associated with an underlying hematologic disorder such as amyloidosis, lymphoma, or myeloma. Within 3 months, he developed paresthesias in his hands and severe ankle weakness. Thereafter, over a period of 3 months he had a rapid neurologic decline and became wheelchair-bound. X-ray of the lesion suggested chronic osteomyelitis, and ultrasonography was nondiagnostic. Neurologic examination showed mild proximal and severe distal weakness in all limbs, absent ankle jerks, and length-dependent sensory loss. Immunofixation was normal, although he previously had an IgG lambda monoclonal protein. Quantitative sensory testing showed lengthdependent dysfunction of large myelinated sensory nerve fibers (abnormal vibration). Blood workup is unremarkable except for mild thrombocytopenia that is probably due to immunosuppressive therapy, and raised prolactin level, which may account for the erectile dysfunction. Temporal dispersion and conduction block are often but not always present, and axonal loss may occur with severity and chronicity. However, both the poor response to immunosuppressive therapy and initial IgG lambda paraprotein are concerning for an alternative etiology. The clinicopathologic features of paraproteinemic neu- ropathies depend on a combination of factors including type of paraprotein (immunoglobulin M, IgG, immunoglobulin A, light chains), underlying disorder (plasmacytoma, myeloma), and associated amyloid deposition. The dramatic neurologic improvement after resection of the bone lesion is noteworthy. Neurosarcoidosis can cause chronic, asymmetric, sensory-greater-than-motor polyradiculoneuropathy. The sural nerve biopsy in this patient showed segmental demyelination (6%) and axonal degeneration (15%) on teased fiber analysis, and moderately reduced myelinated nerve fiber density. Endoneurial edema, epineurial perivascular inflammation, and mild neovascularization were present (figure). Reevaluation of the clavicular biopsy slides with additional immunostaining revealed extensive infiltration of monotypic lambda light chain restricted plasma cells, scattered foamy macrophages, and fibrosis. The nerve biopsy results suggest an inflammatory neuropathy with some demyelinating features. Absence of granulomas makes sarcoid less likely, but there could be proximal granulomas missed on the biopsy. The immunostaining pattern on the clavicular biopsy confirms a lambda-restricted plasmacytoma. Monoclonal protein in the serum is found in about 75% of cases, and associated light chain is almost always lambda. Major long-term disability is due to neuropathy but long-term outcomes have not been studied. Solitary plasmacytoma can be treated with radiotherapy; more extensive disease requires systemic chemotherapy or hematopoietic stem cell transplant. Immunosuppressive treatment in refractory chronic inflammatory demyelinating polyradiculoneuropathy: a nationwide retrospective analysis. He also described recent right foot weakness, numbness in his feet and fingertips, and unintentional 25-pound weight loss over the past year. His medical history was significant for hypertension, gastroesophageal reflux disease, diverticulitis, and pelvic abscesses. Gait examination revealed severe ataxia, a high steppage gait on the right, and a positive Romberg sign. The total ataxia score using the Scale for Assessment and Rating of Ataxia (higher scores indicate increased severity)1 was 14/40, including gait, 5/8; stance, 4/6; sitting, 1/4; speech disturbance, 0/4; finger chase, 0/4; nose-finger test, 0/4; fast alternating hand movements, 2/4; and heel-shin slide, 2/4. Strength testing revealed hip and knee flexion weakness bilaterally (grade 4/5) and severe (grade 2/5) weakness of right ankle dorsiflexion and eversion but preserved inversion strength. Reflexes were brisk in the upper extremities and normal in the lower extremities and plantar responses were flexor. Sensory testing revealed absent lower extremity vibration, absent joint position at the toes, and reduced pinprick in the feet without a sensory level.

Syndromes

• Skin lesion of histoplasmosis
• Radiation therapy to destroy cancerous tissue
• Your doctor or nurse may ask you to wash your hair with a special shampoo the night before surgery.
• Phenobarbital: greater than 40 mcg/mL
• Uvulopalatopharyngoplasty (UPPP) -- to remove excess tissue at the back of the throat. This surgery has not been proven to completely clear up sleep apnea. Long-term side effects are also possible.
• Bladder problems
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• Stool softeners or laxatives to prevent straining during bowel movements
• Wheezing