Mononeuritis multiplex as the first presentation of refractory sarcoidosis responsive to etanercept

BMC Neurology, Dec 2014

Background Several disorders may present with mononeuritis multiplex and the etiological diagnosis can be challenging. Case presentation We report a 42 year-old female who presented with severe lower limb neuropathic pain, asymmetric weakness and sensory impairment and was diagnosed with mononeuritis multiplex. Biopsy showed a granulomatous vasculitic process with eosinophils, scarce granulomata and axonal neuropathy and granulomatosis with poliangiitis was assumed. Steroids, cyclophosphamide, alemtuzumab, azathioprine, mycophenolate mofetil and rituximab were used, all with transient and insufficient response. Skin biopsy performed in a further exacerbation allowed sarcoidosis diagnosis. Infliximab and, later, adalimumab induced good clinical and laboratorial response, but neutralizing antibodies developed to both drugs, so etanercept was tried with good clinical response. Conclusions To the best of our knowledge, this is the first report of sarcoidosis successfully treated with etanercept. This drug may be considered in refractory sarcoidosis after other TNF-α inhibitors failure, having the advantage of not being associated with neutralizing antibodies development.

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Mononeuritis multiplex as the first presentation of refractory sarcoidosis responsive to etanercept

BMC Neurology Mononeuritis multiplex as the first presentation of refractory sarcoidosis responsive to etanercept In?s Br?s Marques 0 Gavin Giovannoni 0 Monica Marta 0 0 Queen Mary University London, Blizard Institute , 4 Newark Street, London E1 1AT , UK Background: Several disorders may present with mononeuritis multiplex and the etiological diagnosis can be challenging. Case presentation: We report a 42 year-old female who presented with severe lower limb neuropathic pain, asymmetric weakness and sensory impairment and was diagnosed with mononeuritis multiplex. Biopsy showed a granulomatous vasculitic process with eosinophils, scarce granulomata and axonal neuropathy and granulomatosis with poliangiitis was assumed. Steroids, cyclophosphamide, alemtuzumab, azathioprine, mycophenolate mofetil and rituximab were used, all with transient and insufficient response. Skin biopsy performed in a further exacerbation allowed sarcoidosis diagnosis. Infliximab and, later, adalimumab induced good clinical and laboratorial response, but neutralizing antibodies developed to both drugs, so etanercept was tried with good clinical response. Conclusions: To the best of our knowledge, this is the first report of sarcoidosis successfully treated with etanercept. This drug may be considered in refractory sarcoidosis after other TNF-α inhibitors failure, having the advantage of not being associated with neutralizing antibodies development. Background Mononeuritis multiplex (MM) can be a manifestation of several disorders including infectious, inflammatory, neoplastic, toxic, metabolic and hereditary conditions, and the etiological diagnosis may be challenging. Rarely, it can be a presentation of sarcoidosis, an inflammatory multisystem granulomatous disease that can involve any part of the nervous system. Peripheral neuropathy is an uncommon manifestation of sarcoidosis patients and presents more frequently with symmetric axonal sensorimotor polyneuropathy, however other manifestations are described, including MM, multifocal motor neuropathy, Guillain-Barr? syndrome, polyradiculopathy, lumbosacral plexopathy, small fibre neuropathy and multiple painful sensory mononeuropathies [ 1-7 ]. Reports of initial presentation with MM are rare [ 3,8,9 ]. Sarcoid neuropathy treatment can also be challenging and, in patients refractory to steroids and imunossupressants, tumor necrosis factor alpha (TNF-α) inhibitors are invaluable [ 10,11 ]. According to literature, infliximab and adalimumab, which bind both soluble and membrane bound TNF-α, seem to be more effective in sarcoidosis than etanercept, which binds only to soluble TNF-α with incomplete inhibition of TNF-α bioactivity [ 12,13 ]. We report a 42-year old female presenting with MM who was eventually diagnosed with sarcoidosis. Tumor necrosis factor alpha (TNF-α) inhibitors were used after steroid and immunosuppressants failure. As neutralizing antibodies (NAbs) against anti-TNF-α antibodies developed, etanercept was tried with good clinical response. This case illustrates how sarcoidosis diagnosis and treatment can represent a challenge and is, to the best of our knowledge, the first report of sarcoidosis successfully treated with etanercept. Case presentation A 42 year-old Afro-Caribbean female presented with severe pain in the lower limbs associated with distal weakness, with progressive worsening during the previous week. Her past medical history was remarkable for longstanding pigmented skin nodules in limbs and torso, bilateral breast implants ten years prior and giving birth to her first child at 26 weeks three months before. Neurological examination revealed tetraparesis (distal upper limbs: grade 4+/5; proximal lower limbs: right = grade 4/5, left = 3/5; distal lower limbs: right = grade 3/5, left = 2/5), absent ankle reflexes, indifferent plantar reflexes, reduced positional sense in left ankle and up to right knee and reduced vibration and superficial pain sense up to both knees. Physical examination identified multiple hyperpigmented small nodules over the limbs and trunk. Investigations Blood workup revealed normocytic anemia, thrombocytosis and increased erythrocyte sedimentation rate (ESR) (110 mm/h), C-reactive protein (CRP) (33 mg/L) and angiotensin converting enzyme (ACE) (74 units/L). Biochemistry including ionogram, calcium, renal and liver function was unremarkable. Syphilis, hepatitis A, B and C and Human Immunodeficiency Virus serologies were negative. Autoimmune studies showed positive antinuclear antibodies (titre > 1/640, speckled pattern) and antineutrophil cytoplasmic antibodies (ANCA) with an atypical cytoplasmic-ANCA (c-ANCA) pattern, however without myeloperoxidaseA (MPO) or proteinase 3 (PR3) specificity. Antinuclear antibodies, antibodies against double stranded DNA, antibodies against extractable nuclear antigens, anti-cardiolipin antibodies and lupus anticoagulant test were negative. Cerebrospinal fluid showed hyperproteino (...truncated)


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Inês Marques, Gavin Giovannoni, Monica Marta. Mononeuritis multiplex as the first presentation of refractory sarcoidosis responsive to etanercept, BMC Neurology, 2014, pp. 237, 14, DOI: 10.1186/s12883-014-0237-5