A 52-year-old man comes to the office due to right leg and left hand weakness. Over the past several days, the patient has had difficulty lifting his right foot when walking, and yesterday, he could not straighten his left wrist or the fingers of his left hand. The patient has also not been feeling well over the past month and reports malaise, intermittent fever, and abdominal pain. He has had an unintentional 2.2 kg (5 lb) weight loss during this period. The patient has no known chronic medical conditions and has not seen a physician for many years. He takes no medications. Temperature is 37.2 C (99 F), blood pressure is 152/90 mm Hg, and pulse is 80/min. Physical examination shows weakness of left wrist and finger extension and right ankle dorsiflexion. There is sensory loss over the dorsum of the left hand and right foot. The abdomen is soft and nontender with no organomegaly. Skin examination findings are shown in the exhibit. Laboratory results are as follows:
| Hemoglobin | 10.1 g/dL |
| Creatinine | 2.2 mg/dL |
| Erythrocyte sedimentation rate | 96 mm/hr |
Which of the following is the most likely diagnosis?
Polyarteritis nodosa | |
Pathophysiology |
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Clinical |
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Diagnosis |
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ANA = antinuclear antibodies; ANCA = antineutrophil cytoplasmic antibodies. | |
This patient has evidence of damage to the radial nerve (wrist-drop, loss of finger extension, dorsal numbness) and deep peroneal nerve (footdrop, foot numbness), indicating mononeuritis multiplex, a neuropathy of ≥2 noncontiguous peripheral nerves. Most cases of mononeuritis multiplex are triggered by underlying vasculitis, particularly polyarteritis nodosa (PAN).
PAN is marked by segmental transmural inflammation of medium-sized muscular arteries, which causes lumen narrowing, thrombosis, and subsequent organ ischemia. Arterial damage tends to be most severe in the following locations:
Neurologic system: Mononeuritis multiplex develops in >70% of patients with PAN due to damage to arteries supplying large peripheral nerves. Most cases are marked by asymmetric polyneuropathy, but progressive disease can lead to symmetric nerve involvement.
Skin: Several skin manifestations are linked to PAN, including livedo reticularis (reddish-blue, net-like pattern, as seen in this patient), erythematous nodules, and palpable purpura.
Renal system: Almost all patients with PAN have renal insufficiency due to renal artery narrowing, thrombosis, and infarctions.
Gastrointestinal system: Damage to mesenteric arteries can cause abdominal pain, mesenteric ischemia, and bowel perforation.
Patients with PAN tend to have very high levels of circulating inflammatory cytokines, which frequently causes constitutional symptoms (eg, malaise, intermittent fever, weight loss), elevated inflammatory markers (eg, erythrocyte sedimentation rate), and anemia of chronic disease. Because PAN is not typically associated with antineutrophil cytoplasmic antibodies (seen in granulomatosis with polyangiitis and microscopic polyangiitis) or high titers of antinuclear antibodies (seen with certain autoimmune conditions), the diagnosis generally requires tissue biopsy.
(Choice A) AL amyloidosis is marked by the deposition of monoclonal light chains in tissue. Patients frequently have nephrotic syndrome, purpura (particularly in a raccoon pattern around the eyes), and compressive peripheral neuropathy (eg, carpal tunnel syndrome). Because amyloid is non-inflammatory, an elevated erythrocyte sedimentation rate and intermittent fever are unusual. In addition, livedo reticularis is uncommon.
(Choice B) Disseminated Lyme disease frequently causes radiculoneuritis and cranial neuropathy. However, the rash associated with Lyme disease is an annular lesion with central clearing that slowly spreads outward (erythema migrans); it is not livedo reticularis. In addition, abdominal pain and renal failure are uncommon.
(Choice D) Syphilis can cause systemic, dermatologic, and neurologic manifestations. However, cranial neuropathy or meningovascular neuropathy, rather than mononeuritis multiplex, are typical of neurosyphilis; and the classic rash of secondary syphilis is a diffuse maculopapular rash involving the palms and soles. Renal failure is uncommon.
(Choice E) Systemic sclerosis generally causes skin thickening/hardening and renal insufficiency. However, peripheral neuropathy is a rare complication, and livedo reticularis is atypical.
Educational objective:
Polyarteritis nodosa often causes mononeuritis multiplex, a neuropathy of ≥2 noncontiguous peripheral nerves. Patients also frequently have skin, renal, and gastrointestinal manifestations; the lungs are generally spared.