|Year : 2020 | Volume
| Issue : 4 | Page : 316-319
A neuro-immunological cocktail
K Nikitha1, Sachin Sureshbabu2, Remesh Bhasi3, LK Sreevidya2
1 Department of General Medicine, Aster MIMS Hospital, Kozhikode, Kerala, India
2 Department of Neurology, Aster MIMS Hospital, Kozhikode, Kerala, India
3 Department of Rheumatology, Aster MIMS Hospital, Kozhikode, Kerala, India
|Date of Submission||17-Apr-2020|
|Date of Acceptance||05-Oct-2020|
|Date of Web Publication||24-Dec-2020|
Dr. Sachin Sureshbabu
Department of Neurology, Aster MIMS Hospital, Kozhikode, Kerala
Source of Support: None, Conflict of Interest: None
This report describes the story of a young female, diagnosed with the rare combination dermatomyositis and myasthenia gravis (MG). The patient presented with progressive muscle weakness without typical skin manifestations of dermatomyositis, except for an early mechanic's hand. In addition, the patient had fatiguability and mild ptosis which raised the suspicion of MG which was later confirmed by the presence of anti-acetyl choline receptor antibodies and clinical response to pyridostigmine. On evaluation, she was found to be seropositive for Mi-2Beta antibody, which is a myositis-specific antigen for classical steroid responsive dermatomyositis.
The following core competencies are addressed in this article: Medical knowledge, Patient care, Practice based learning and improvement.
Keywords: Anti Mi-2Beta antibody, anti-synthetase syndrome, dermatomyositis, inflammatory muscle disease, myasthenia gravis
|How to cite this article:|
Nikitha K, Sureshbabu S, Bhasi R, Sreevidya L K. A neuro-immunological cocktail. Int J Acad Med 2020;6:316-9
| Introduction|| |
Inflammatory muscle disease is an entity with a wide spectrum of clinical subtypes including pure polymyositis, dermatomyositis, overlap syndrome, anti-synthetase antibody syndrome, inclusion body myositis, and so on. There can be co-existing autoimmune diseases in these patients involving entirely different proteins, an expression of the hyperactive immune system in these subjects. This narration is about a 39-year-old female, who presented with fatiguable weakness and clinical features of a connective tissue disorder. With no consistent electrophysiological abnormalities, the diagnosis of a co-existent myasthenia gravis (MG) with dermatomyositis was confirmed with established seropositivity for acetylcholine and Mi-2Beta receptors, respectively.
| Case Report|| |
A 39-year-old female, apparently healthy 1 year prior to the presentation, came with complaints of slowly progressive weakness of upper limbs. She reported difficulty in wringing clothes and combing hair. The weakness was worse during evening hours and was aggravated by physical activity and exertion. She had no difficulty in holding a tumbler or writing. She had minimal difficulty with walking, in getting up from the bed while there was no history suggestive of distal lower limb weakness. She also gave a history of difficulty in chewing which is brought about a few minutes into the act. There was neither difficulty experienced while swallowing, speaking nor was there any diplopia or drooping of eyelids apparent to the relatives. No symptoms were reported pertaining to the sensory or autonomic systems.
For the past 6 months, she has breathing difficulty; modified Medical Research Council (mMRC) Grade 1 to start with gradually progressed to mMRC Grade 3 over 3 months. There were no other cardio-respiratory symptoms such as cough, wheeze, epistaxis, hemoptysis, chest-pain, palpitations, paroxysmal nocturnal dyspnea, or orthopnea. She also had a history of dryness of mouth and Raynaud's phenomenon for about a year. No history of prolonged fever, skin rashes, joint pain, or early morning stiffness.
On examination, there was thickening and fissuring of both palms, suggestive of early mechanic's hand. She also had very restricted mouth opening, which could be attributed to her thick and tight skin. Cranial nerve examination was normal, except for mild ptosis. There was significant weakness in the proximal muscles with a manual muscle testing-8 score of 76. Deep tendon reflexes were normal and plantars were flexor bilaterally. There were no sensory or cerebellar signs. Fatiguability was also demonstrable clinically. Arm abduction time and leg rising time were significantly increased. However single breath count was preserved, enabling her to count up to 24, in a single breath. There were no signs of active synovitis involving any of the joints. Systemic examination was noncontributory except for fine crackles in bilateral lung bases.
On evaluation, her routine blood investigations showed microcytic hypochromic anemia. ANA profile showed positivity to SS-A/Ro 52 while rheumatoid factor, anti-CCP, and serum complement levels were normal. The myositis profile showed strong positivity for Ro-52 and PM-Scl 75 and borderline positivity for anti-Ku antibodies and was suggestive of an overlap syndrome – probably scleroderma–polymyositis overlap. Taking into account the fatiguability and diurnal variation, with no major stigmata of systemic illness, she was evaluated for MG. Repetitive nerve stimulation (RNS) and nerve conduction study were however negative. However, she was started on pyridostigmine, to which she positively responded. Later, seropositivity to acetylcholine receptor antibodies was established. To rule out other cardiorespiratory causes of dyspnea, she was further investigated. Computed tomography thorax showed subtle ground glassing in the bilateral posterior basal segments of the lungs, consistent with early interstitial lung disease (ILD), with no mediastinal mass – ruling out thymoma simultaneously. Diffusion capacity of lung for carbon monoxide also showed mild diffusion defect. However, echocardiogram was normal with no features of pulmonary hypertension nor were there clinical features of hypoxemia. Ultrasonogram abdomen done to rule out any internal malignancy associated with her autoimmune illness detected no significant abnormality.
She was treated with pulse steroid therapy for 5 days, tapered slowly over a few months. Immunomodulators (mycophenolate mofetil and hydroxychloroquine) and pyridostigmine were added. She was also initiated on limb physiotherapy and muscle strengthening exercises.
She was kept under close follow-up, to look for the evolution of her disease. She remained asymptomatic throughout the course. Myositis profile was repeated after 1 year. Seropositivity to Mi-2Beta antigen was established, suggesting the diagnosis of dermatomyositis, the classical steroid responsive variant, with a good prognosis.
| Discussion|| |
Immunological disorders affecting the neuromuscular apparatus share several common clinical features which have to be differentiated meticulously to ascertain the accurate clinical localization. Adding to the clinical challenge is the existence of overlap syndromes involving multiple parts of the neuraxis with or without systemic involvement [Table 1]. The clinical scenario presented here is of a progressive pure motor syndrome with preserved reflexes and relatively subtle cranial nerve involvement on a backdrop of suspected systemic autoimmune illness. The two possible localizations in this context would be: Muscle versus neuromuscular junction. The latter was suggested by the presence of mild ptosis and fatiguability. However, the presence of systemic stigmata pointed to the diagnosis of probable idiopathic inflammatory myopathy (IIM) as per the ACR/EULER classification for IIM with a probability of >55%. The odd features mentioned definitely needs to be accounted for and there was not supporting evidence for the same on 2 Hz RNS. The clinical response to pyridostigmine and acetylcholine receptor (AChR) antibody positivity however conclusively established the presence of this immune disorder overlap - dermatomyositis with MG. Through this clinical narrative, the authors wanted to highlight the importance of suspecting multilevel neuromuscular involvement in the presence of clinical clues not fitting into the prototype of a single part involvement (muscle or nerve or neuromuscular junction).
The complexity of the case lies in the evolving nature of the disease as well as its ability to evade every effort to define the exact phenotype. The presence of Mi 2 positivity and muscle weakness favors dermatomyositis, but there is a conspicuous absence of typical dermatologic features, such as Gottron's papules, heliotrope rash, or Gottron's sign. On the other hand, the patient satisfies the clinical criteria for anti-synthetase syndrome (ASS), except for the absence of anti-synthetase antibodies (anti-PL-7, anti-PL-12, anti-EJ, anti-OJ, anti-KS, anti Zo, anti-Ha). In addition, ILD is more common in ASS compared to primary dermatomyositis (DM). The presence of scleroderma like skin changes gives the flavor of an overlapping nonspecific phenotype. Nevertheless, the specific antibody identified, confirmed our diagnosis of DM, despite all the aforementioned atypicalities.
The existence of these DM with MG phenotypes simultaneously in a single patient has been described previously but the antibody status of the subjects was infrequently explored in the previous reports. Paik et al. studied six such patients in whom two patients were antibody positive, one for PM-Scl and anti-P 155/140 while four of them fulfilled the clinical criteria for dermatomyositis. Fatigable weakness was present in 5/6 while other features such as dysphagia, ptosis, and dysarthria were present in ≤50% thus underscoring the importance of the former symptom in clinching the diagnosis. Four of them were antibody positive and thymic neoplasia was seen in 50% %and thymoma was detected in none. This observation coupled with ours probably shows that the immune process leading to this overlap syndrome may not have a paraneoplastic basis. This is in sharp contrast to PM associated MG which has a strong association with thymoma. Mathis et al., in a case report had presented 2 cases of neuromyositis, both of which had MG simultaneously diagnosed with another autoimmune disease. Both of them had anti-AchR antibody positivity, thymoma-negative MG with electrophysiology revealing overlapping features subacute inflammatory neuropathy and myositis. Van de Warrenburg et al. reported a case of inflammatory myositis with MG presenting with respiratory insufficiency and ophthalmoplegia. The diagnosis was made based on clinical features and biopsy consistent with inflammatory myositis. However, no specific antibody positivity could be established. There is only one previous report of a 69-year-old man with Anti MI-2 positive DM and MG overlap. In this report also, MG was the fore runner with DM evolving over few years. However, the dermatological manifestations were more classical in him and the clinical response to steroids was unsatisfactory which required the use of intravenous gamma globulin to arrest the clinical progression. Anti-Mi-2 is an immunological marker of classic DM which is generally associated with good response to steroid treatment and good prognosis.
| Conclusion|| |
Immune-mediated illnesses are difficult to define in its entire spectrum as they evolve over time and span over systems. This narrative elaborates on one such account where the syndromic diagnosis continued to challenge us because of discordance between clinical features and immunological profile. The challenges in diagnosis as well as the importance of clinical judgment and heightened suspicion are emphasized in this rare simultaneous occurrence of DM and MG. The hyperactive immune response can prove detrimental to many different proteins, manifesting as varied systemic symptoms. The co-existence of NMJ disorder with autoimmune inflammatory muscle disorder in this patient emphasizes the same.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
Research quality and ethics statement
The authors of this manuscript declare that this scientific work complies with reporting quality, formatting and reproducibility guidelines set forth by the EQUATOR Network. The authors also attest that this clinical investigation was not determined to require Institutional Review Board/Ethics Committee review.
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