|Ahead of print publication
The weeping heart, the choked lung, the blinded eye, and the crying femur: A saga of juvenile dermatomyositis
Arun Hegde1, Suchi Acharya2, Subramanian Shankar3, Abhishek Kumar4, Uday Bhanu Kovilapu5
1 Department of Rheumatology, Command Hospital (Southern Command), Pune, Maharashtra, India
2 Department of Pediatrics, AFMC, Pune, Maharashtra, India
3 Department of Rheumatology, Army hospital (Research and Referral), Delhi cantt, Air Cmde AFMS (P&T), O/o DGAFMS, New Delhi, India
4 Department of Rheumatology, Command Hospital (Eastern Command), Kolkata, West Bengal, India
5 Department of Radiodiagnosis, AFMC, Pune, Maharashtra, India
|Date of Submission||01-Mar-2021|
|Date of Acceptance||12-Mar-2021|
Department of Pediatrics, AFMC, Wanowrie, Pune - 411 040, Maharashtra
Source of Support: None, Conflict of Interest: None
Juvenile dermatomyositis (JDM) is the most common inflammatory myositis in children that primarily involves the skeletal muscles and skin. However, it can manifest with a diverse range of clinical features across multiple organ systems. JDM vasculopathy causing optic neuritis and medullary bone infarcts in children are rare manifestations of JDM and have been seldom reported in literature. Similarly, cardiovascular manifestations in the form of refractory myocarditis leading to congestive cardiac failure during the early course of the disease have also been rare findings. Early diagnosis and aggressive management of such complications using biological disease-modifying synthetic antirheumatic drugs has significantly reduced the mortality and morbidity associated with JDM. Herein, we report a mini case series of three patients with JDM who presented with these rare systemic manifestations and achieved favorable outcomes while being managed using the Childhood Arthritis and Research Alliance-Treatment Protocols.
Keywords: Bronchiolitis obliterans organizing pneumonia, calcinosis, childhood arthritis rheumatology and research alliance, juvenile dermatomyositis, rituximab
|How to cite this URL:|
Hegde A, Acharya S, Shankar S, Kumar A, Kovilapu UB. The weeping heart, the choked lung, the blinded eye, and the crying femur: A saga of juvenile dermatomyositis. Indian J Rheumatol [Epub ahead of print] [cited 2021 Dec 9]. Available from: https://www.indianjrheumatol.com/preprintarticle.asp?id=323368
| Introduction|| |
Juvenile dermatomyositis (JDM) is an autoimmune disease primarily associated with muscle and skin involvement with vasculopathy being an inherent component in its pathogenesis, resulting in extra muscular manifestations involving the gastrointestinal (GI) tract, heart, and lung, portending a poor prognosis. It differs from adult-onset myositis, as evidenced by a higher incidence of GI vasculitis, calcinosis, and lipodystrophy. The incidence of JDM is about 3.2 cases per million children per year. The average age at onset is 7 years with a slight female preponderance (female:male ratio: 2:1). The classification criteria for JDM that were initially proposed by Bohan and Peter in 1975 have become outdated with the advent of magnetic resonance imaging (MRI) and recently, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) proposed modified criteria which require the presence of the pathognomic skin rash of JDM with at least three of the following: (1) muscle weakness, (2) elevation of muscle enzymes, (3) abnormal electromyogram (ECG) suggestive of inflammatory myopathy, (4) muscle biopsy suggestive of inflammatory myopathy, and (5) MRI evidence of myositis to classify a case as JDM. We, herein, present three cases of JDM that were diagnosed using the above criteria and highlight the myriad and rare clinical features and the successful outcomes achieved in these cases
| Case Reports|| |
Our first patient was an 11-year-old girl, second born to a nonconsanguineous marriage. She presented to the hospital with complaints of alopecia, photosensitive rash on the face and hands, recurrent oral ulcers, and Raynaud's phenomenon of 4 months duration, which was preceded by fever and polyarthritis of the small joints of both hands at the onset. She was brought to the hospital in a bedbound state and on detailed inquiry, parents provided a history of a progressive decline in her functional activity resulting in an inability to get up from squatting position along with difficulty to comb her hair over the past 1 month. General examination revealed an emaciated (weight-22 kg, body mass index [BMI] – 12.1 kg/m2, both <3rd percentile) and ill-looking child with tachypnea, tachycardia, and hypotension along with a raised jugular venous pressure. Skin examination revealed cutaneous ulcer [Figure 1], Gottron papules [Figure 1], and malar rash crossing the nasolabial folds. Musculoskeletal (MSK) examination revealed polyarthritis involving small joints of both hands, wrists, and knees with a swollen joint count of 8, tender joint count of 10, and proximal muscle weakness (Grade 3/5) of both upper limb and lower limb, along with truncal and neck weakness. Auscultation revealed bilateral basal crackles, third heart sound, and a pansystolic murmur at the left lower sternal border. Her investigations are summarized in [Table 1]. Two-dimensional echocardiography revealed features of myocarditis with congestive cardiac failure (CCF) in the form of global hypokinesia, severe left ventricular (LV) systolic dysfunction (ejection fraction – 25%), and dilated ventricles, along with severe mitral and moderate tricuspid regurgitation [Figure 2]. High-resolution computed tomography (HRCT) of the chest was suggestive of interstitial lung disease (ILD) (bronchiolitis obliterans pattern [BOOP]). The patient was managed with pulse intravenous methylprednisolone (IVMP) at 30 mg/kg, hydroxychloroquine (HCQS) at 200 mg/day, and other supportive measures in the form of diuretics and inotrope support. However, the response to initial therapy was muted and on day 4 of admission, the patient developed refractory tachycardia (>160 beats/min) along with hypotension, finally culminating in a cardiopulmonary arrest from which she was successfully revived. Over the next few days, she was dependent on mechanical ventilation due to frequent episodes of pulmonary edema and she sustained one more cardiac arrest. The treatment was intensified and she was given intravenous immunoglobulin (IVIG) at 2 g/kg along with steroids (1 mg/kg) and was also commenced on rituximab (375 mg/m2)/weekly regime (planned for a total of 4 weeks). Over the 2nd week of admission, the patient gradually showed an improvement in ejection fraction and was successfully weaned off inotrope support and mechanical ventilation. On the 18th day of hospitalization, the patient complained of severe pain in the abdomen localized to the right iliac fossa accompanied by few bouts of vomiting and hematochezia. Contrast-enhanced computerized tomography (CT) of the abdomen was done which revealed thickening of the appendix. Further, CT angiography was also done which revealed features of GI vasculitis in the form of punctate hemorrhages and mural edema. Colonoscopy revealed multiple punched-out ulcers in the colon with active bleeding spots. She received a second cycle of pulse methylprednisolone and rituximab was continued. In the course of hospital stay, the patient also developed digital gangrene [Figure 3] and punched-out ulcers on the dorsum of left third metacarpophalangeal joint and buttocks, along with calcinosis. CARRA clinical treatment protocol was followed in view of refractory nature of disease and she received IVIG every 2 weeks, for three doses, followed by monthly doses, along with maintainance immunosuppression in the form of subcutaneous methotrexate (MTX) 15 mg/wk. She exhibited signs of improving muscle power at the end of 2 months and could sit up in the chair. At 3 months of admission, she was able to walk to the toilet with support. She subsequently received monthly IVIG for 6 months and also received 6 monthly rituximab for a further three cycles, after which it was stopped and only maintainance immunesupression with MTX and oral steroids in tapering doses were continued. In her 3rd year of follow-up, she presented to the hospital with severe pain in the lower part of both thighs with an inability to bear weight without any features of muscle weakness or knee arthritis. A repeat MRI of thighs revealed medullary infarcts in both femurs [Figure 4]. Evaluation for antiphospholipid antibodies was negative. Prednisolone doses were increased with recovery in symptoms. By the 4th year of follow-up, she gradually regained complete muscle strength along with a complete resolution of calcinosis and normalization of cardiac functions and also gained height. She could be successfully tapered off DMARDs (Disease modifying antirheumatic drugs) completely, after 5 years, and remains symptom-free now at 7 years of follow-up.
|Figure 1: (Case 1) – Cutaneous ulcers on extensor aspects (black arrow) of hand and Gottron papules over knuckles (orange arrows)|
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|Figure 2: Two-dimensional echocardiography (Case 1) shows severe left ventricular systolic dysfunction. (Left ventricular ejection fraction 25%), dilated left ventricular cavity (Black arrows), and mild pericardial effusion (Red arrows)|
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|Figure 4: Magnetic resonance imaging (both thighs) in Case 1 shows STIR coronal sequences showing intramedullary hyperintensities involving both distal femur in geographic pattern with narrow zone of transition suggestive of bone infarcts (Black arrows)|
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A 12-year-old girl, firstborn to a nonconsanguineous marriage, presented to the hospital with sudden-onset painless loss of vision in the right eye that occurred 7 days prior to presentation to the hospital, which she noticed on getting up from sleep in the morning. There was no history of trauma, redness, diplopia, or fatiguability. She also gave a history of polyarthritis of small joints of the hands, myalgia, nonitchy dusky rash over the knuckles, and Raynaud's phenomenon for the previous 4 months. On examination, she was cachectic (weight – 25 kg, BMI – 13.1 kg/m2, both <3rd percentile). Dermatological examination revealed Gottron papules. MSK examination revealed polyarthritis involving the wrist, knee, and small joints of the hand and feet. There was a Grade 4/5 weakness in the proximal muscles of all four limbs. Eye examination revealed decreased visual acuity (perception of light only) in the right eye. Fundus examination of the right eye revealed a pale optic disc. The rest of the systemic examination was unremarkable. The investigations are summarized in [Table 1]. Visual-evoked potential showed grossly delayed and low amplitude pattern in the right eye suggestive of optic neuritis. A possibility of neuromyelitis optica spectrum disorder was considered and was ruled out by a normal serum aquaporin-4 immunoglobulin G antibody profile, a normal cerebrospinal fluid oligoclonal band profile and a normal (without any features of demyelination) MRI of the brain, orbit, and spinal cord. Thus, finally, a diagnosis of JDM complicated with retrobulbar optic neuritis was established and the child was aggressively managed with pulse IVMP (30 mg/kg) for 5 days with gradual improvement in vision to finger counting at two feet and then initiated on maintenance therapy with oral prednisolone (1 mg/kg/day) along with weekly subcutaneous MTX (15 mg/wk) and HCQS (200 mg/day). On follow-up at 1 year, the muscle weakness, arthritis, and rash had subsided completely and vision in the right eye had improved to 6/6.
A 15-year-old girl, firstborn to a nonconsanguineous marriage, presented to the hospital with myalgia, alopecia, oral ulcers, rash on the knuckles and face, and Raynaud's phenomenon of 6 months' duration. Over the past 2 months, she had also developed exertional dyspnea and also had been running moderate grade fever over the past week along with a painful left knee swelling. There was also a history of weight loss of 10 kg over the past 6 months. At admission, she was febrile and had tachycardia. Her weight and BMI were less than the 3rd percentile. She had Gottron papules over the knuckles, heliotrope rash, and malar rash. MSK examination revealed left knee arthritis, proximal muscle weakness (power –3/5, at both hip and shoulder joints), and associated neck muscle weakness. Chest and cardiovascular examination were normal. Her salient investigations are summarized in [Table 1]. Synovial fluid aspirated from the left knee grew Staphylococcus aureus on culture. HRCT of the chest revealed BOOP of ILD [Figure 5]. She was evaluated for immunedeficiency; however, her immunoglobulin profile and complement levels were normal. The girl was diagnosed with JDM complicated by septic arthritis and ILD. She was managed with intravenous antibiotics (ceftriaxone, vancomycin, and amikacin) for 14 days, followed by oral prednisolone (1 mg/kg/day), along with MTX (15 mg/wk SC) and HCQS (200 mg/day). She showed good response to treatment with complete improvement in muscle power.
|Figure 5: High-resolution computed tomography (Chest) in Case 3 shows axial images in lung window revealing patchy subpleural ground glass opacities; small consolidation in right middle lobe and apical segment of right lower lobe, features suggestive of interstitial lung disease|
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| Discussion|| |
In JDM, vasculopathy plays the central role in the pathogenesis of cutaneous, MSK, and other systemic manifestations such as intestinal ischemia, perforation, ILD, and myocarditis. Sytemic involvement carries a poor prognosis and its early identification and aggressive management with corticosteroids and conventional/biological disease-modifying antirheumatic drugs forms the backbone of care in such cases. This case series highlights the several rare vasculopathic manifestation of JDM in the form of intestinal hemorrhage, myocarditis with CCF, ILD, medullary bone infarcts, and retrobulbar neuritis. These complications are rarer and are virtually unreported occurring together in the same patient.
JDM is associated with a wide range of skin manifestations like the pathognomic heliotrope rash, gottron papules, cutaneous ulcers and gangrene., Papadopoulou and McCann in their review article reported that cutaneous ulceration affects 20%–30% of children with JDM and these lesions often reflect a more severe disease course. In the present series, case1 had cutaneous ulcerations and digital gangrene along with major internal organ involvement with a very severe and protracted disease course.
Cardiac complications have been reported in children with JDM but are extremely rare (0%–3%), particularly at the onset of disease; however subclinical cardiac involvement in JDM is not an uncommon finding. Schwartz et al. in their case–control echocardiographic studies in children with JDM have found that up to 25% of patients had evidence of subclinical LV diastolic dysfunction and a high prevalence of pathological ECG abnormalities. Clinically, serious cardiac dysfunctions such as pericarditis, conduction block, myocarditis, or myocardial infarction leading to arrhythmias and CCF during the early course of JDM have rarely been demonstrated in JDM. We encountered fulminant myocarditis with CCF (case 1) during the initial presentation of the disease itself, which is a clinical rarity.
Eyes represent another organ that can be affected by JDM vasculopathy. Retinopathy or retinal vasculitis has been reported in a fair number of JDM cases, but optic neuropathy in JDM is very rare., To the best of our knowledge, it has never been reported in children with JDM. Cohen et al. and Foroozan in their study reported optic neuropathy in dermatomyositis, but those were adult patients.
In our series, case 1 also developed bilateral medullary infarcts of the femur during her follow-up period, the cause of it could be attributed to prolonged steroid therapy or the vasculopathy itself. To the best of our knowledge, bony infarcts in children with JDM have never been reported before, although it has been sparingly reported in adults with polymyositis and SLE.,
Pulmonary involvement (≈8%) is much less common in children with JDM than the adult, but ILD may still complicate childhood cases. Hence, expert groups recommend a baseline evaluation for lung function in all children with JDM. Papadopoulou and McCann in their review reported that lung involvement in JDM may vary from asymptomatic BOOP to more life-threatening conditions such as diffuse alveolar hemorrhage and pneumomediastinum. In the present series, cases 1 and 3 manifested radiological features of BOOP. Case 1 was also found to be positive for anti-Ro 52 antibodies. Anti-Ro-52 antibody can be seen in 5%–15% of patients of dermatomyositis and has been associated with ILD.
| Conclusion|| |
JDM can present with diverse clinical manifestations across multiple organ systems. Early recognition of these varied clinical presentations along with optimum immunosuppression can lead to a significant reduction in morbidity and mortality with improved functional outcomes.
Written informed consent was obtained from parents of all patients. Besides, all children provided assent.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, parents of all patients have given their consent for images and other clinical information to be reported in the journal. Parents understand that names and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
All the medicines and investigations were free of cost since the study was carried out in a government hospital.
Conflict of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]