SLR- January 2014- Laksha Dutt
Reference: Wolf J, Schmitt V, Palm F, Grau AJ, Bergner R. Peripheral Neuropathy as Initial Manifestation of Primary Systemic Vasculitides.
Scientific Literature Review
Reviewed By: Laksha Dutt, DPM
Residency Program: Madigan Army Medical Center
Podiatric Relevance: Non-diabetic related peripheral neuropathy is a very common complication in patients with primary systemic vasculitides. Historically, due to low incidence of primary systemic vaculitides, there is little published on the clinical manifestation, therapy options, and outcome for patients with vasculitis peripheral neuropathies. This article evaluates newly diagnosed patients with primary systemic vasculitis and associated vasculitic neuropathy at onset of the disease using a standardized neurological evaluation.
Methods: From January 2002-December 2010, patients newly diagnosed with a primary systemic vasculitis from eosinophilic granulomatosis with polyangitis (EPGA, Churg Strauss Vasculitis), polyarteritis nodosa (PAN), microscopicpolyangiitis (MPA), and granulamatosis with polyangiitis (GPA) were enrolled in a prospective study. Diagnosis was made by a rheumatologist and those patients were exclusively screened by neurologists. Patients included in the study were those who presented with symptoms of peripheral neuropathy at the time of diagnosis, when peripheral neuropathy was caused by vasculitis and there was no other disease processes causing peripheral neuropathy (i.e. diabetes, alcoholism, VitB12 deficiency). Patients were evaluated at the time of diagnosis, at three months and six months with rheumatologist and neurologist, respectively. Activity of disease process was measured using the Birmingham Vasculitis Activity Score (BVAS) at time of diagnosis and during follow-up and ranges from from 0 to 63 with higher scores indicated more severe disease activity. When both clinical and electrophysiolgical abnormalities were detectable, the diagnosis of peripheral neuropathy was made. Patients were required to have reduced orabsent ankle reflexes and reduced distal vibration sense or a reduced superficial tactile sensation (cotton wisp) for symmetrical polyneuropathy. Alternatively, multiplex mononeuropathy diagnosis was made based on weakness ofmuscles supplied by a single nerve. In electrophysiological studies, nerve conduction studies require reduced or absent bilateral sensory and/or muscleaction potentials with or without alterations of conduction velocity. In addition to diagnosis peripheral neuropathy, the study distinguishes between axonal and demyelinating neuropathyusing electrodiagnostic criteria. The degree of disability due to neuropathy was measured at the first diagnosis and during follow-up using the functional disability scores (DS).
Results: Of a total of 89 patients with primary systemic vasculitis, 22 patients were diagnosed with peripheral neuropathy. There was no significant difference in age at diagnosis and BVAS score with patients with and without neuropathy. Out of the 22 patients, 14 were seen in the department of neurology showing peripheral neuropathy as the first sign of the disease process. In 18 out of 22 patients, biopsy was performed to complete the clinical criteria. Two patients had anisolated sural nerve biopsy which showed no vasculitis changes. Two patients had an isolated muscle biopsy showing positive result of transmural infiltration by inflammatory cells andnecrosis of cell walls. Three patientsthat had a combined nerve and muscle biopsy showed positive results. Peripheral neuropathy was detected in 12 of the 20 patients with EPGA, in 6 of the 47 GPA patients, in one patient with MPA, and in three patients with PAN with a total of 22.
This study also compared the different types of peripheral neuropathy: mononeuropathia multiplex (MNM) vs symmetrical polyneuropathy(PNP). Out of 22 patients, 13 were diagnosed with MNM while nine patients were diagnosed with PNP with the sidenote that patients with PNP tended to be older at disease onset than patientswith MNM. In all 22 patients,electromyographic testing that was conducted showed axonal neuropathy. In 13 patients with MNM, the frequency of involvement of the Peroneal nerve was 69 percent ,Sural nerve 62 percent, Posterior tibial nerve 54 percent, Median nerve 38 percent, Ulnar nerve 31 percent, radial nerve 23 percent and sciatic nerve at 8 percent. This study showing that the lower extremity nerves were affected more than the nerves supplying the upper extremities.
Pain due to the vasculitis neuropathy was registered in 13 out of the 22 patients (59 percent) with pain being localized in the region ofthe involved nerves. Due to the high frequency of nerve involvement in the lower extremities, pain was localized mainly in lower extremities. The initial disease activity score (BVAS) was also measured during initial diagnosis andfollow-up. Patient with MNM had greater disease activity measuring at 21 while those with PNP had a lower score of 17. Inflammatory markers were more elevated in patients with MNM compared to patients with PNP.
Therapy was based on the extent of organ involvementand guidelines of the national neurological and rheumatological societies. First line of treatment was corticosteroids with cyclophophamide being the second line of treatment for those with more severe cases. Three patients out of the 22 were further treated with rituximabfor B cell depletion. Out of the 13 patients with painful neuropathy, 11 had pain decreased below three points after starting corticosteroid therapy. After 12 months of therapy, the median of DS in patients with MNM improved from three to two and in patients with PNP from three to one. Although patients did show improvement in the DS during follow-up, the axonal damage was persistently found in all patients both clinically and by electromyography.
Conclusion: This study shows that either mononeuropathy multiplex (MNM) or symmetric polyneuropathy (PNP) can be the first symptom in patients with primary systemic vasculitis. Although the incidence of primary systemic vasculitis is rare, it is important to keep an open mind when treating a patient presenting with vasculitic neuropathy. Nerves affected in vasculitic neuropathy are predominately in the lower extremity which is similar in presentation to the general uncontrolled insulin-dependent diabetic patient. As foot and ankle physicians, it is our goal to keep in mind that diabetes is not the only cause for neuropathy and there are many more diseases process that leads to neuropathy (Vit B12 deficiency, alcoholism, monoclonal gammopathy). Given the complexity of the neurological disease process for patients with primary systemic vasculitis, a multidisciplinary approach to treatment involving both rheumatologist and neurologist will be beneficial to the patient.