12.12.2013
by Nancy Walsh
Staff Writer, MedPage Today

Peripheral neuropathy is a more common manifestation of systemic lupus erythematosus (SLE) than has been previously appreciated, and often is a small-fiber neuropathy affecting the dorsal root ganglia, a large retrospective study found.

In a 25-year study of 2,097 patients, 82 had SLE-specific peripheral neuropathy, which in 17.1% was diagnosed as a small-fiber rather than axonal neuropathy — a finding that isn’t even included in the American College of Rheumatology (ACR) case definition for neuropsychiatric SLE, according to Julius Birnbaum, MD, of Johns Hopkins, and colleagues.

And unlike most small-vessel neuropathies, which have a characteristic “stocking and glove” distal pattern of involvement, the majority of affected SLE patients had a highly unusual pattern of pain in the torso, face, proximal extremities, and even the whole body, the researchers reported online in Arthritis & Rheumatism.

“We report on findings in a large cohort of well characterized SLE peripheral neuropathy patients, with our identification of an overlooked entity of small-fiber neuropathy suggesting that expansion and revision of the ACR neuropsychiatric case definitions are warranted,” they stated.

The past decade has seen a marked increase in the understanding of central nervous system manifestations of SLE such as headache, seizures, and mood disorders and how these manifestations are associated with clinical disease and autoantibodies, but awareness of peripheral neuropathy has remained limited.

In 1999, the ACR published case definitions for the neuropsychiatric manifestations of SLE, but diagnostic advances since that time have allowed more precise identification of disease features, such as small-fiber neuropathies that have been reported in other inflammatory conditions such as Sjogren’s syndrome.

Therefore, to more clearly delineate these disease manifestations, Birnbaum and colleagues conducted a chart review of patients enrolled in the Hopkins Lupus Cohort, identifying 218 who had some type of neuropathy.

After excluding those whose neuropathy could be explained by other diagnoses such as metabolic and infectious causes, they identified 66 who were at high likelihood of having SLE-specific neuropathy, and 16 with a modest likelihood.

Electrodiagnostic studies were used to identify axonal and demyelinating neuropathies, and skin biopsies with immunostaining were employed to detect decreases in small-fiber nerve density.

Of the 82 patients with SLE-related neuropathy, 14 had small-fiber neuropathies. There was only one patient with the acute demyelinating neuropathy Guillain-Barre syndromeand only one with a plexopathy — conditions both of which are included in the ACR neuropsychiatric criteria.

The small-fiber neuropathies included two distinct types. Only five of the 14 patients had the classic stocking-and-glove type, which typically begins as burning pain in the feet and also affects the hands. The remaining nine exhibited an “entirely different and unorthodox pain distribution.”

In patients with the feet/hands pattern, skin biopsies determined that the lower density of intra-epidermal nerve fibers was limited to the distal leg, and was considered as representing axonal degeneration.

In those with the distinct, wider distribution, the biopsy-proven nerve fiber decrease was more commonly found in the thigh than in the distal leg, indicating degeneration of the dorsal root ganglia.

“Our findings reinforce that rheumatologists who care for patients with SLE should be aware of how to recognize and diagnose a small-fiber neuropathy, particularly since a small-fiber neuropathy may occur in the face of normal electrodiagnostic studies,” Birnbaum and colleagues observed.

The researchers then considered possible correlations between peripheral neuropathy and other disease and patient characteristics, and found that patients with neuropathy differed from those without neuropathy in having later onset disease, at age 34 versus 29.

Patients with neuropathy also had lower disease activity, with mean disease activity scores of 2.2 compared with 2.8 for those without neuropathy (P=0.01), but higher disease damage as evaluated on the Systemic Lupus International Collaborating Clinics (SLICC)/ACR damage index (4 versus 1.9, P<0.01).

There also were significantly higher rates of specific comorbidities in patients with peripheral neuropathy:

• Herpes zoster infection, 37.8% versus 16.2% (P<0.01)
• Opportunistic infections, 45.7% versus 24.8% (P<0.01)
• Pneumonia, 42.7% versus 27.8% (P=0.03)
• Oral candidiasis, 32.9% versus 18.3% (P<0.01)
• Osteopenia, 75.9% versus 44.5% (P<0.01)
• Osteoporotic fractures, 46.3% versus 21.1% (P<0.01)

On multivariate analysis, SLE-associated peripheral neuropathy was significantly associated with herpes zoster, opportunistic infections, and osteoporotic fractures (P<0.01 for all).

These comorbidities can be associated with the immunosuppressive treatments used for SLE, but the researchers noted that in their cohort, patients with neuropathy had received similar doses of corticosteroids as those without neuropathy.

“Our findings suggest that SLE neuropathy patients should be aggressively screened for osteoporosis,” the researchers advised.

They also cautioned against assuming that SLE patients with “seemingly improbable pain patterns” have a non-organic pain syndrome, emphasizing that a small-fiber neuropathy may explain the symptoms.

A limitation of this analysis was its retrospective nature.