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Table of Contents
Year : 2016  |  Volume : 19  |  Issue : 3  |  Page : 424-426

Simultaneous occurrence of scleroderma, neuromyotonia, and inflammatory myopathy: Evidence of common immunological etiology

1 Department of Neurology, All India Institute of Medical Sciences, New Delhi, India
2 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India

Date of Submission23-Oct-2015
Date of Decision15-Nov-2015
Date of Acceptance17-Dec-2015
Date of Web Publication25-Jul-2016

Correspondence Address:
Manjari Tripathi
Department of Neurology, All India Institute of Medical Sciences, New Delhi - 110 029
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0972-2327.179977

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How to cite this article:
Dash D, Kumar M, Suri V, Padma MV, Tripathi M. Simultaneous occurrence of scleroderma, neuromyotonia, and inflammatory myopathy: Evidence of common immunological etiology. Ann Indian Acad Neurol 2016;19:424-6

How to cite this URL:
Dash D, Kumar M, Suri V, Padma MV, Tripathi M. Simultaneous occurrence of scleroderma, neuromyotonia, and inflammatory myopathy: Evidence of common immunological etiology. Ann Indian Acad Neurol [serial online] 2016 [cited 2021 Aug 1];19:424-6. Available from:


Neuromyotonia is a rare condition of spontaneous continuous muscle activity, characterized by muscle twitching at rest (myokymia), cramps triggered by voluntary muscle contraction, and impaired muscle relaxation. We report this unique case of neuromyotonia with localized scleroderma along with histopathologically proven inflammatory myopathy. Neuropathological findings suggest a common immunologic process targeting the peripheral nervous system and skin.

A 33-year-old young man, presented with history of a hyperpigmented skin lesion that started from the dorsal surface of the left forearm and then progressively involved the whole of left upper limb and left thigh region over a period of 10 years. In addition, he reported a sensation of rippling in the left shoulder region for the last 4 years that gradually progressed to involve the left thigh. It was associated with spontaneous painful spasms of left hand and forearm. He noticed in addition, difficulty in opening his fist while milking his buffaloes for the last 4 years. These symptoms progressively started interfering with his activities of daily living. Additionally, he gave a history of recurrent left shoulder dislocation for the last 4 years. There was no history suggestive of cranial nerve involvement, weakness of any limbs or sensory complaints, bladder or bowel complaints, breathlessness, oral ulcers, renal, cardiac or pulmonary involvement, diabetes, and hypertension. Examination revealed a hyperpigmented band of sclerotic skin over the dorsal aspect of left arm, forearm, and left thigh [Figure 1]. Neurological examination revealed myokymia in the left deltoid, biceps, triceps, vastus lateralis, and glutei with grip myotonia in the left hand with dystonic posturing of the left upper and lower limb with painful spasms. The rest of the neurological examination was normal. A working diagnosis of morphea with myotonia was kept and the patient was further investigated.
Figure 1: Photograph of the hyperpigmented band of sclerotic skin over the dorsal aspect of left arm and forearm

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Biochemical investigations revealed normal hematology, calcium, and liver function test. His creatine phosphokinase (CPK) was 151 U/L (normal 40-226 U/L). Results of nerve conduction studies and repetitive nerve stimulation test (to rule out associated neuromuscular junction disorder) were normal. Examination by needle electromyography of the deltoid and triceps showed spontaneous grouped discharges recurring semirhythmically at a rate of 2 to 10 Hz. The motor unit action potentials (MUAPs) were of small amplitude and short duration with an early and full recruitment in both deltoid, triceps, left vastus lateralis, and tibialis anterior. The biopsy of the skin revealed flattening of the epidermal rete ridges. The papillary and reticular dermis showed dense sclerosis and collagenization with pulling up of adnexal structures. In the lower dermis, mature lymphocytes were noted infiltrating the wall of small and medium-sized vessels. Other than the lymphocytic vasculitis, no fibrinoid necrosis was identified. Based on the histomorphological findings a diagnosis of morphea with lymphocytic vasculitis was made. Biopsy of the right vastus lateralis muscle was performed. The overlying skin had no clinical evidence of scleroderma. After snap freezing the biopsy with isopentene in liquid nitrogen, multiple frozen sections were taken and a series of enzyme-histochemistry and immunohistochemical stains were performed. The muscle biopsy showed well-maintained fascicular architecture. Occasional atrophic fibers were interspersed in-between. There were moderately dense chronic inflammatory cell infiltrates in and around the endomysial capillaries [Figure 2]. Enzyme histochemistry [nicotinamide adenine dinucleotide-tetrazolium reductase (NADH-TR), adenosine triphosphatase (ATPase) pH 9.4, and succinate dehydrogenase (SDH)] showed normal fiber type distribution. Immunohistochemical stain for major histocompatibility complex (MHC) class I showed strong membranous positivity, while that for MHC class II was negative. Immunostain for major attack complex (MAC) showed positivity in the endothelium of endomysial capillaries. Based on the histomorphological findings, a diagnosis of inflammatory muscle disease was made.
Figure 2: Photomicrograph of muscle biopsy demonstrating perimyseal perivascular chronic inflammatory cell infiltrate, H & E ×100

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He was initially managed on intralesional triamcinolone, Psoralen ultraviolet A (PUVA), and pulse dexamethasone therapy but these was no benefit. Patients were given trial of oral steroids and azathioprine but did not show much improvement. After the neurological evaluation and biopsy findings the patient was given a trial of five cycles of plasmapheresis after which there was a significant reduction in the myokymia.

Neuromyotonia is a disease with peripheral nerve hyperexcitability with accumulating evidence for autoimmune origin over the last few years. This was first suggested by Newsom Davis et al. in the early 1990s. [1] Morphea represents a spectrum of clinical entities ranging from localized scleroderma to systemic sclerosis. The cutaneous lesions eventually evolve from a sclerotic stage to a indurated stage, and residual hypopigmentation or hyperpigmentation follows. [2] The lesions are characterized by bands or plaques of fibrous pigmented skin involving mainly the extremities. There have been previously reported cases where patients had localized scleroderma along with neuromyotonia in the same segment. [3] There has been suggestions in literature that scleroderma affects subcutaneous and deeper tissues, including muscles, ligaments, and bone, leading to stretching, angulation, or compression of nerves, followed by focal demyelination of motor nerve fibers. This may lead to nerve hyperexcitability and thus can present with neuromyotonia or dystonia akin to hemifacial spasm. [4]

Our case would be the first to demonstrate the association of neuromyotonia with inflammatory myopathy in presence of localized scleroderma. Additionally, our patient had histopathological evidence of inflammatory myopathy with strong immunopositivity for MHC class I. Electrophysiological features additionally suggested features of myopathy with normal CPK. Thus, the possibility of neuromyotonia occurring due to nerve entrapment or secondary to the mechanical effects of skin changes due to scleroderma is less likely. We hypothesize the possibility of a common factor triggering the immunological system. This is further supported by the presence of inflammatory cells of MHC class I cell type in muscle in skin tissue. It suggests a delayed type hypersensitivity and most likely there may be a common driving mechanism that is altering the self-identification of the immunological system. Neuropathological findings in localized scleroderma as well provide evidence for an underlying inflammatory process rather than a vascular dysgenetic origin as a causative pathogenic pathway. Histologically, all lesions reported till date suggest inflammatory and possibly autoimmune pathology. [5],[6]

The response of the patient to plasmapheresis additionally gives a further boost to our hypothesis. This report thus provides evidence for a probable common immunological factor triggering the cascade of all the three diseases.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Newsom-Davis J, Mills KR. Immunological associations of acquired neuromyotonia (Isaacs' syndrome). Report of five cases and literature review. Brain 1993;116:453-69.   Back to cited text no. 1
Peterson LS, Nelson AM, Su WP. Classification of morphea (localized scleroderma). Mayo Clin Proc 1995;70:1068-76.   Back to cited text no. 2
Kumar A, Jain R, Daga J. Simultaneous occurrence of neuromyotonia and morphoea: A cause-effect relationship? J Neurol Neurosurg Psychiatry 2006;77:802.   Back to cited text no. 3
Cruccu G, Inghilleri M, Berardelli A, Pauletti G, Casali C, Coratti P, et al. Pathophysiology of hemimasticatory spasm. J Neurol Neurosurg Psychiatry 1994;57:43-50.   Back to cited text no. 4
Zulian F, Athreya BH, Laxer R, Nelson AM, Feitosa de Oliveira SK, Punaro MG, et al.; Juvenile Scleroderma Working Group of the Pediatric Rheumatology European Society (PRES). Juvenile localized scleroderma: Clinical and epidemiological features in 750 children. An international study. Rheumatology (Oxford) 2006;45:614-20.   Back to cited text no. 5
Takehara K, Sato S. Localized scleroderma is an autoimmune disorder. Rheumatology (Oxford) 2005;44:274-9.  Back to cited text no. 6


  [Figure 1], [Figure 2]


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