A 52-year-old man is evaluated for a 1-year history of progressive weakness that began as right foot drop and bilateral tingling in the feet. Within the past 2 months, the patient has developed progressive weakness, which makes walking difficult; he also notes weakness in the hands and burning below the knees but no autonomic symptoms. He has hypothyroidism treated with levothyroxine.
On physical examination, vital signs are normal. Motor strength is 4/5 in the intrinsic hand and quadriceps muscles and 3/5 in the tibialis anterior and gastrocnemius muscles; bulbar and facial muscle strength is normal. Deep tendon reflexes are absent in the lower extremities. Sensory perception of vibration is severely impaired at the knees. Pinprick testing shows reduced sensation below the ankles. Splenomegaly is present, as are patchy areas of hyperpigmentation and scattered angiomas on the trunk. Gait is broad based and wobbly, and a Romberg test has positive results.
Serum immunofixation reveals a λ light chain monoclonal protein.
Needle electromyography reveals a demyelinating sensorimotor polyneuropathy.
Which of the following is the most likely diagnosis?
A. Amyotrophic lateral sclerosis
B. Chronic inflammatory demyelinating polyradiculoneuropathy
C. Mitochondrial myopathy
D. POEMS syndrome
MKSAP Answer and Critique
The correct answer is D. POEMS syndrome. This item is available to MKSAP 18 subscribers as item 27 in the Neurology section. More information on MKSAP is available online.
The most likely diagnosis is POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes). POEMS syndrome is characterized by the presence of a monoclonal plasma cell disorder, peripheral neuropathy, and one or more of the following: osteosclerotic myeloma, Castleman disease (angiofollicular lymph node hyperplasia), elevated serum vascular endothelial growth factor, organomegaly, endocrinopathy, edema, typical skin changes, and papilledema. His clinical presentation, including splenomegaly, skin lesions (hyperpigmentation and angiomas), endocrine disease (hypothyroidism), peripheral neuropathy, and λ monoclonal gammopathy support the diagnosis of POEMS syndrome. POEMS syndrome is typically secondary to an underlying cancer; identification and treatment of the underlying cancer leads to improvement of the neuropathy.
Amyotrophic lateral sclerosis (ALS) is characterized by upper motor neuron signs (such as hyperreflexia, spasticity, and an extensor plantar response) coexistent with lower motor neuron findings (such as atrophy and fasciculation). Sensory deficits are characteristically absent, and sensory nerve conduction studies are often normal in ALS. These findings are not consistent with this patient's presentation.
The classic presentation of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is generalized areflexia and progressive or relapsing symmetric sensory and motor neuropathy. CIDP resembles POEMS syndrome in its neurologic manifestations, but the presence of monoclonal gammopathy, splenomegaly, and skin changes makes this diagnosis unlikely.
Mitochondrial myopathy can present with significant variability and may cause fatigue, myalgia, ophthalmoplegia, and various extramuscular manifestations. Mitochondrial myopathies should be suspected in the presence of multiorgan involvement and maternal transmission. In this patient, the presence of sensory deficits and neuropathic findings on needle electromyography are not consistent with a myopathy.
- POEMS syndrome is characterized by the presence of a monoclonal plasma cell disorder, peripheral neuropathy, and one or more of the following: osteosclerotic myeloma, Castleman disease (angiofollicular lymph node hyperplasia), elevated serum vascular endothelial growth factor, organomegaly, endocrinopathy, edema, typical skin changes, and papilledema.