Egad!

A 69-year-old woman presented to the clinic with pain in the right great toe lasting several days. She was prescribed colchicine and indomethacin empirically for gout. She took one tablet of colchicine (0.6 mg) every hour until her stools became loose after the eighth tablet. Her toe pain resolved, but two days later she developed bilateral lower extremity pruritus and paresthesia and presented to the emergency department (ED). On physical examination, no rash, weakness, or sensory deficits were observed, and she was able to ambulate without assistance. Her patellar reflexes were normal. The complete blood count was notable for an absolute lymphocyte count of 6,120/µL (normal: 1,100-4,800), and the comprehensive metabolic panel was normal. Serum creatine kinase (CK) was 341 U/L (normal: 24-170) and uric acid 7.7 mg/dL (normal: 2.4-6.4). Her lower extremity symptoms were attributed to colchicine, which was discontinued. She was prescribed diphenhydramine and discharged home.

Monoarthritis of the hallux is the classic manifestation of gout, although other considerations include pseudogout, sesamoiditis, and trauma. The typical side effects of colchicine include diarrhea and myositis. Colchicine-induced muscle injury often results in a modest elevation of CK levels and is associated with myalgia.

Paresthesia is defined as abnormal sensory symptoms that most commonly localize to the peripheral nerves or spinal cord. Acute neuropathies or myelopathies might result from vasculitis, heavy metal toxicity, vitamin deficiencies, and paraneoplastic neurologic syndromes. The normal motor, sensory, and reflex examination, however, make these unlikely.

The neuro-anatomic localization of pruritus is poorly understood but is proposed to include peripheral nerves, spinothalamic tracts, and thalami. Acute pruritus (lasting <6 weeks) typically results from a primary dermatologic process such as a drug reaction, eczema, or xerosis. Less common causes include uremia, cholestasis, and thyroid disease. Pruritus can also be seen with malignancy, most commonly hematologic or paraneoplastic syndromes, or with connective tissue diseases. At this stage, it is unclear whether her pruritus and paresthesia are part of a unifying disease process.

Five days later she re-presented to the ED with nausea and emesis after eating at a restaurant. Her symptoms improved with intravenous fluids, and she was discharged. Four days later she returned with difficulty ambulating, bilateral leg cramping, and continued pruritus and paresthesia. The chemistry panel was normal except for a potassium level of 2.6 mmol/L and a bicarbonate level of 32 mmol/L. She was admitted to the hospital because of severe hypokalemia and impaired ability to ambulate. Her potassium was replenished. Her CK was elevated (3,551 U/L on hospital day 7). She was given cyclobenzaprine, gabapentin, oxycodone, acetaminophen, and prednisone (40 mg); her cramping only mildly improved, and she remained unable to walk. On hospital day five she had visual hallucinations and confusion, which did not resolve with administration of haloperidol; a head CT was unremarkable. On hospital day eight the patient, with her family’s support, left the hospital and presented to a different ED for a second opinion.

Difficulty ambulating often results from weakness, sensory impairment, cerebellar ataxia, extrapyramidal dysfunction (eg, parkinsonism), and pain. In this patient, leg cramping suggests pain or true weakness due to a myopathic process as a contributing factor. Symptoms of muscle disease include cramps, myalgia, and difficulty walking. Causes of elevated CK and myalgia include inflammatory myopathies, endocrinopathies, drugs, infections, and electrolyte abnormalities (eg, hypokalemia). Her age and acuity of presentation decrease the likelihood of a metabolic myopathy due to a disorder of glycogen storage, lipid metabolism, or mitochondrial function. Her hypokalemic metabolic alkalosis likely resulted from vomiting. Hypokalemic periodic paralysis is unlikely as exacerbations typically only last hours to days. As such, her difficulty ambulating, muscle cramps, and elevated CK strongly support a primary myopathic disorder, although additional information regarding the neurologic examination is still required.