Rheumatoid Arthritis Complicated by Myositis and Vasculitic Neuropathy: A rare link
The case of 36-year-old rheumatoid arthritis (RA) patient who was diagnosed with myositis and vasculitic neuropathy was published in the Journal of Association of Physicians of India (JAPI).
The case identified the rare connection between vasculitis and myositis with RA and identified that rheumatoid arthritis focal weakness may be due to severe underlying circumstances such as vasculitis.
The 36-year-old man, a known case of rheumatoid arthritis for four years, was admitted with progressive painless proximal weakness of both legs over the last three months. He was a manual laborer who carried a lot of weight every day. But because of this new onset symptom, he had to leave his job. Also, for the last month, he complained of weakness of small muscles of foot of the right leg. He had difficulty in wearing chappals. There was no significant atrophy of muscles anywhere in the legs. The man was on regular hydroxychloroquine, methotrexate, and leflunomide for his rheumatoid arthritis. Also, occasionally, he used oral steroids (over the counter) for relief of joint pain.
The man had no joint pain although the fingers of the hands were deformed. Power of hip flexion was 2/5 bilaterally and power around knee joint was 4/5. There was a gross weakness of ankle dorsiflexion and toe flexion on the right side; the left side was normal. Although the patient did not complain of any sensory symptoms, sensation to all modalities were reduced on the right side up to mid-calf. On the left side, only an isolated patch of sensory loss around the ankle was found. Knee jerks were normally present bilaterally; ankle jerk was absent on the right side and reduced on the left. There was no muscle tenderness anywhere. There was no weakness in any other muscle, including extra-ocular muscles. Skin rash was absent. Ophthalmoscopy did not reveal any retinal lesions.
Initial laboratory investigations revealed hemoglobin of 8.7 gm/dl, total leukocyte count of 11000/µL (neutrophil 80%) and platelet count of 2.5 lakh/µL. ESR was 72 mm in the 1st hour and CRP level was 53.8 mg/L (N<6). Serum rheumatoid factor was 88 IU/L (N<20) and the anti-CCP level was >200 IU/L (N<5). Anti-nuclear factor, complement levels, ANCA, and cryoglobulin tests were all negative. Serum CPK level was just elevated at 320 IU/L . Blood viral serology for HIV, hepatitis B, C, CMV, and blood vitamin B12 levels were normal. Oral glucose tolerance test and kidney function tests were also normal. Anti-Ach-R antibodies were negative. Urine analysis did not show any proteinuria. Nerve conduction velocity study showed the axonal type of sensori-motor polyneuropathy in both lower limbs (right>left). Upper limbs were normal. Electromyography revealed a myopathic pattern with polyphasic potentials. Arterial Doppler study did not show any evidence of vasculitis is the large vessels.
After consultation with a multi-disciplinary group, a muscle biopsy was done from the vastus lateralis muscle which showed (Figure 1) partial atrophy of muscle fibres with perifascicular aggregation of inflammatory lymphoplasmacytic cells, suggestive of active inflammation. This biopsy report could explain the proximal weakness of the legs. However, that could not explain the distal sensori-motor symptoms and signs. So, afterwards, a nerve biopsy was also done from the right sural nerve. This showed (Figure 2) intense inflammatory cell infiltration in the nerve fibres around blood vessels with karyorrhexis. Thus, the patient was finally diagnosed to have inflammatory myopathy and also, neuropathy due to small vessel vasculitis. He was given two doses of rituximab (1000 mg, 14 days apart) and oral prednisolone (1 mg/kg). The proximal weakness improved quickly with power 4-/5 around hip after one month. But, the distal weakness and sensory loss persisted at 6 months’ follow up. However, after starting the immunosuppressive regimen, the symptoms/signs of neuropathy have not progressed. Also, he has not developed any new clinical features of vasculitis. The DMARDs for rheumatoid arthritis are being continued as before.
Vasculitis in RA can manifest as skin lesions like purpura, pyoderma or ulcers, peripheral nervous system (PNS) involvement like polyneuropathy or Mononeuritis multiplex or it can involve internal organs with potentially more serious consequences.1 In PNS involvement, nerve biopsy has a very high diagnostic yield. Biopsy usually reveals intense perivascular inflammatory cell aggregation inside the nerve3. Biopsy is usually diagnostic but sometimes, electrophysiological studies may provide the initial suggestion of vasculitic neuropathy. Electrophysiological studies may show different patterns in RA. A study from Western India have shown that the electrophysiological patterns in RA can be pure sensory or pure motor or mixed and of either axonal or demyelinating variety.4 Usually, long duration of RA is associated with the development of vasculitic neuropathy.4
Myositis is rare, compared to vasculitis, in RA patients. Like vasculitis, this also occurs in long standing RA cases, but occasionally, myositis can be the presenting feature of RA.5 The myositis can involve appendicular muscles, as in this case or exceptionally, it may involve atypical locations like extra-ocular muscles6. The diagnostic approach of myositis in RA is similar to idiopathic polymyositis cases, i.e. EMG study, blood enzyme levels and muscle biopsy, either alone or in combinations.
Vasculitis in RA is treated with steroids, cyclophosphamide or the biological therapies like TNF-α inhibitors.1 These can be used singly or in combination. But, the treatment response is often variable and unpredictable.1 Since the treatment is still evolving, different treatment groups have different protocols. In this case, the authors used rituximab, followed by oral steroids. the author's choice of this particular regimen was also prompted by the co-existence of myositis. Since RA myositis is very rare, there is no definitive guideline on its management. But in the reported cases, authors have documented good response with high-dose oral steroids. In this case too, the proximal muscle weakness improved quickly with steroids. But the neuropathy was very slow to respond.
Nowadays, anti- TNF-α biologicals are commonly used for RA. There has been some reports of the development of myositis and neuropathy after TNF-α inhibitor use.7,8 Hence, if a patient of RA develops such features, prior drug history should always be enquired into to rule out a drug-induced etiology. In this case, there was no history of the use of biologicals.
The co-existence of myositis and vasculitis in RA is very rare in the medical literature. There is only one other case similar to the present case, reported from the USA.9 In that case, a 62-year-old man presented with Mononeuritis multiplex and proximal weakness. The joint disease was clinically mild at the time of presentation, like this case. Final diagnosis, in that case, was also established by biopsy of muscles and nerve
Focal weakness in rheumatoid arthritis can be caused by severe underlying circumstances such as vasculitis. Such instances should, therefore, be researched carefully and therapy quickly initiated for better results, the authors conclude.
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