Vasculitic neuropathy following exposure to minocycline

Patient 1.

A 17-year-old otherwise healthy girl awoke with new-onset arm pain, numbness, and weakness in the left ulnar nerve distribution. She had a history of acne for which she had taken minocycline for 3 years. Eleven days after development of the left arm symptoms, she developed numbness over the lateral aspects of the bilateral feet and thighs.

She was seen by an orthopedist who believed she had a compressive left ulnar neuropathy at the elbow and, on day 31 after symptom onset, she underwent a left ulnar nerve transposition. Left arm pain and weakness worsened postoperatively. A month later, the patient developed acute left leg weakness, nausea, and vertigo, which prevented her from walking. On examination, she demonstrated left arm and bilateral ankle dorsiflexion weakness and reduced sensation in the left hand and bilateral feet.

Subsequent brain MRI showed an acute right medial medullary ischemic stroke. Extensive evaluation did not reveal a hypercoagulable state, embolic source, or large artery abnormality. Nerve conduction studies and needle EMG showed diffuse abnormalities within all limbs, which were asymmetric and suggestive of an axonal multiple mononeuropathy or asymmetrical polyradiculoneuropathy. Left upper extremity findings localized to the brachial plexus or multiple peripheral nerves. A brachial plexus MRI showed generalized increased T2 signal intensity throughout the course the left brachial plexus. Antinuclear antibody (ANA) was mildly positive (1:160) and C-reactive protein was elevated (18.4). CSF analysis was normal. Autoimmune and infectious workups were otherwise negative. A left superficial radial nerve biopsy was consistent with necrotizing vasculitis (figure 1).

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Figure 1 Patient 1 radial nerve biopsy

(A) Hematoxylin & eosin stain of radial nerve demonstrates epineurial nerve large arteriole necrotizing vasculitis. Note the prominent inflammatory cell infiltrate infiltrating and disrupting all layers of the arteriolar wall and the fibrinoid necrosis (arrows). (B) Methylene blue stain of radial nerve demonstrates myelinated fiber degeneration in the center of the fascicle that is typical of ischemic changes (outlined).

Following diagnosis, minocycline was discontinued. The patient was started on IV methylprednisolone and azathioprine. On follow-up several months after discharge, she demonstrated good clinical improvement with regard to pain, strength, and sensation.

Patient 2.

A 33-year-old man was seen in consultation for evaluation of left foot pain and weakness. The patient had a several month history of recurrent episodes of generalized muscle soreness, joint pain, and fatigue. Episodes would last up to several days at a time. The most severe episode occurred in conjunction with a fever (103°F), chills, cold sweats, low back pain radiating to the right testicle, and acute left leg and foot pain and paresthesias. He had been taking minocycline for acne for 2 years. Strength examination was normal apart from mild left foot inversion, ankle plantarflexion, and toe weakness. There was reduced sensation to vibration at the left toe and reduced pinprick at the sole of the left foot.

An ANA was mildly positive (1:160) and a thyroid peroxidase antibody level was elevated (19.34). Autoimmune and infectious workups were otherwise negative. No imaging was performed. Electrophysiology studies demonstrated an isolated left, subacute, primarily axonal, tibial mononeuropathy. A left gastrocnemius muscle biopsy was consistent with necrotizing vasculitis (figure 2).

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Figure 2 Patient 2 gastrocnemius muscle biopsy¹⁰

Gomori trichrome stain of gastrocnemius muscle biopsy shows large arteriole necrotizing vasculitis.

Following diagnosis, the minocycline was discontinued. The patient was initiated on high-dose oral prednisone and IV cyclophosphamide. At 3-month follow-up after diagnosis, he demonstrated clinical improvement of strength and pain. His constitutional symptoms had fully resolved.

Patient 3 (previously reported).

A 28-year-old woman presented for evaluation of weakness, pain, and paresthesia in the left foot.⁴ She was previously healthy other than starting minocycline 2 weeks prior for treatment of acne vulgaris. Minocycline was discontinued shortly after symptom onset.

On examination, there was distal left foot weakness involving both peroneal and tibial distributions and diminished sensation in the left sciatic territory. Electrophysiology studies demonstrated a left sciatic mononeuropathy with active denervation in both peroneal and tibial innervated muscles. Serologic testing demonstrated positive ANA and SSA. The remainder of autoimmune and infectious workups was negative. A lumbosacral plexus MRI demonstrated mild increased T2 hyperintensity of the bilateral L4-S1 nerve roots with extension into the femoral and sciatic nerves. A left sural nerve biopsy was consistent with necrotizing vasculitis, with multifocal myelinated fiber loss as well as large and small perivascular inflammatory cell collections in both the endoneurium and epineurium.

After cessation of minocycline, the patient was started on a 1 g per week 12-week IV methylprednisolone treatment session. She was seen in follow-up at 3 months, by which time her strength and gait had returned to normal.