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)