Differentials

Marfan syndrome

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Family history of sudden collapse, aortic aneurysm, aortic dissection, and valve pathology suggestive.

Marfanoid habitus is characteristic and necessary for diagnosis. Features include: high arched palate; arachnodactyly; pectus excavatum or carinatum; scoliosis; arm span to height ratio >1.05; tall stature with reduced upper segment to lower segment (US/LS) ratio of <0.85; foot length (heel to first toe) to height ratio >0.15; hand length (wrist crease to third finger) to height ratio >0.11.[23]

Lens dislocation, neurologic abnormalities of the pelvis and lower limbs suggesting peripheral nerve entrapment (dural ectasia), and signs of pneumothorax (tracheal deviation, decreased air entry on affected side) may be present.

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Aortic regurgitation and aortic root dilation are common findings on echocardiogram; may also reveal ascending aortic dissection.

MRI of the lumbar spine may show dural ectasia.

Molecular analysis of peripheral blood sample shows fibrillin I and II abnormalities.

Pneumothorax and emphysematous bullae on chest x-ray may be noted.

Fibromyalgia

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Chronic pain syndrome diagnosed by the presence of widespread body pain (front and back, right and left, both sides of the diaphragm) for at least 3 months, in addition to fatigue, waking unrefreshed, and/or cognitive symptoms.[34]

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Diagnosis is clinical.

Myalgic encephalomyelitis (chronic fatigue syndrome)

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Characterized by persistent fatigue and other associated symptoms (e.g., musculoskeletal pain, sleep disruption, memory impairments) lasting at least 6 months. The fatigue is not related to other medical conditions, disease processes, or identifiable biologic causes. Sleep, rest, and activity restriction do not improve symptoms.

Patients may present with a low-grade fever, tender lymph nodes, muscle pain/joint stiffness on palpation, tachycardia, hyperventilation, and/or orthostatic hypotension.

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Diagnosis is clinical.

Loeys-Dietz syndrome

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Autosomal dominant genetic syndrome that has many features similar to Marfan syndrome.[35]

Pronounced skeletal deformities have been reported in children. Key skeletal elements include club feet, scoliosis, upper cervical deformity, and knee or elbow hyperextensibility. Presence of hypertelorism, cleft palate, or bifid uvula should prompt referral to a geneticist.[35]

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Genetic testing reveals mutations in the genes encoding transforming growth factor beta receptor 1 or 2.

Aortic root dilation is a common finding on echocardiogram

Thrombotic thrombocytopenic purpura

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Neurologic exam might reveal focal abnormalities, and presence of pallor (anemia) and petechiae can support the diagnosis.

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Examination of the peripheral smear is critical and shows evidence of microangiopathic hemolytic anemia with fragmented red blood cells (schistocytes) and thrombocytopenia.

Idiopathic thrombocytopenic purpura

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Isolated thrombocytopenia in the absence of other causes; thought to be due to an autoimmune phenomenon. Typically found in middle-aged women, often with a preceding viral illness, who present with thrombocytopenia with or without bleeding.

Physical exam is usually normal. Petechiae may be present on mucosal membranes or the lower limbs.

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CBC and smear shows isolated thrombocytopenia.

von Willebrand disease

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Usually presents with mucocutaneous bleeding.

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Diagnosis is based on various tests, including von Willebrand factor (VWF) antigen, VWF activity (ristocetin cofactor or collagen-binding assay), factor VIII assay, and VWF multimers.

Corticosteroid excess

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One of the most common causes of poor wound healing; history of chronic corticosteroid use usually present.

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Diagnosis is clinical.

Porphyria cutanea tarda

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Results from an acquired, substantial deficiency of uroporphyrinogen decarboxylase in the liver.

Recognized by blistering and crusted skin lesions on the back of hands and other sun-exposed areas of the body. Other common features include skin fragility with minor trauma causing blister formation, hypertrichosis, skin hyperpigmentation, and dark or reddish urine.

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High plasma and urine total porphyrins.

Epidermolysis bullosa

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Inherited mechanical fragility of the skin and epithelial tissues. Presents as recurrent erosions, blisters, and scars.

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Diagnosis is confirmed by immunofluorescence antigen mapping performed on a cryopreserved skin biopsy specimen, obtained from a freshly induced lesion.

Vitamin C deficiency

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Scurvy is a rare disorder, with epidemics typically affecting populations subject to famine or displacement during wartime.

Most key clinical manifestations are related to impaired collagen synthesis. These include bleeding complications (spontaneous petechiae and ecchymoses), friable gingiva and loose teeth, bone pain, and joint effusions.

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Low levels of serum, leukocyte, and whole blood ascorbic acid confirm the diagnosis.

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