Juvenile dermatomyositis: a case of delayed recognition with unusual complication of nephrocalcinosis

Abstract

Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy in children and is characterised by the presence of proximal muscle weakness, heliotrope dermatitis, Gottron’s papules and occasionally auto antibodies. The disease primarily affects skin and muscles, but can also affect other organs. Renal manifestations though common in autoimmune conditions like lupus are rare in JDM. We describe a child whose presenting complaint was extensive calcinosis cutis. Subtle features of proximal muscle weakness were detected on examination. MRI of thighs and a muscle biopsy confirmed myositis. Nephrocalcinosis was found during routine ultrasound screening. We report the first case of a child presenting with rare association of dermatomyositis, calcinosis cutis and bilateral medullary nephrocalcinosis.

Background

Juvenile dermatomyositis (JDM) is a rare systemic immune-mediated disease of childhood, with a classic combination of proximal muscle weakness, elevated muscle enzymes and typical skin manifestations. The estimated incidence is 2–4 per million children per year and prevalence of 2.5/100 000.¹ It is a potentially life-threatening condition in children with severe disease, but with prompt diagnosis and advent of aggressive immunosuppressive therapy, outcomes are much better and long-term survival rate in JDM children is >95%.² The most common complication in JDM is calcinosis, affecting up to 40% of patients and is associated with severe skin disease.³ Ulcerations and calcinosis can be challenging to treat and may cause long-term morbidity and impact the quality of life in patients with JDM.

Case presentation

A 7-year-old boy presented to paediatric out-patient department with a history of painful nodular swelling over his elbow joints (figure 1), forearms and legs for the past 7 months. Though his parents did not complain of obvious symptoms related to musculoskeletal system, they admitted that the boy had mild difficulty getting up from squatting posture and climbing stairs. He had no history of fever, rashes, breathing difficulty or medication intake. His antenatal and postnatal history was uneventful. His developmental milestones were appropriate for his age. He had no significant family history. On examination, his height and weight were in 50th to 75th percentile. He had a faint erythematous skin lesion over face and chest. There were no typical Gottron’s papules or heliotrope rash of JDM. Numerous tender nodular swelling of 0.5×0.5 cm were present over various sites including elbows, forearms, knee joints and shin of tibia. Gower’s sign was positive suggestive of proximal muscle weakness. A complete musculoskeletal examination was performed, which revealed weakness of his neck, arm and thigh muscles bilaterally. The Childhood Myositis Assessment Scale (CMAS) was 40/52. Manual Muscle Testing of 8 groups of muscles score was 68/80. Capillary nail fold assessment showed dilated and tortuous capillaries. Based on this history and clinical assessment, JDM with calcinosis cutis was suspected.

Figure 1.

Calcinosis nodules over the elbow.

Investigations

A baseline complete blood count, erythrocyte sedimentation rate (ESR) and renal function tests were normal. Creatinine phosphokinase (CPK), lactate dehydrogenase (LDH) and alanine transaminase (ALT)/aspartate transaminase (AST) levels were normal. Antinuclear antibody test was negative. Myositis specific antibodies were not requested because of non-availability. X-rays of his limbs revealed extensive calcinosis cutis (figure 2). A quadriceps muscle biopsy showed dense infiltrate of lymphocytes admixed with plasma cells between the muscle bundles mainly in the regions of perimysium (figure 3). MRI of his thighs revealed severe inflammation and calcification of the muscles (figure 4). With these investigation findings, diagnosis of JDM was confirmed.

Figure 2.

X-ray showing extensive calcinosis over upper and lower limbs.

Figure 3.

Quadriceps muscle biopsy showing dense infiltrate of lymphocytes admixed with plasma cells between the muscle bundles.

Figure 4.

MRI thighs showing severe muscle oedema with calcinosis.

As part of routine work-up, abdominal ultrasound was performed and this revealed bilateral medullary nephrocalcinosis (figure 5). We considered hypervitaminosis D, primary hyperparathyroidism, hypercalciuria, renal tubular acidosis, hyperuricaemia, hyperoxaluria and hypocitraturia in the differential diagnosis for nephrocalcinosis. Investigations including urine analysis, 24 hours urine calcium, uric acid, oxalate and citrate, arterial blood gas analysis, renal function test, serum electrolytes, calcium, albumin, phosphorous, magnesium, 25 hydroxy vitamin D and parathyroid hormone levels were normal.

Figure 5.

Ultrasonogram (USG showing medullary nephrocalcinosis.

Treatment

The patient was started on prednisolone 2 mg/kg, weekly subcutaneous methotrexate injections 15 mg and monthly disodium pamidronate infusions 1 mg/kg. Alkali therapy in the form of potassium citrate was advised for nephrocalcinosis along with water intake of minimum 2 L/day to prevent super saturation of crystalluria producing substances.

Outcome and follow-up

At 6 months follow-up, signs of muscle weakness had resolved and his CMAS had improved to 50/52. Calcinosis cutis had improved but not completely resolved. Follow-up ultrasound showed persistent nephrocalcinosis. Currently, the child continues to receive low dose steroids with methotrexate for JDM, parenteral pamidronate for calcinosis cutis and potassium citrate for nephrocalcinosis.

Discussion

Dermatomyositis is a systemic connective tissue disorder that often involves autoimmune dysregulation. It is marked by long-term inflammation of small blood vessels, muscles and skin. Children with JDM commonly present between the ages of 5 and 15 years. The disease can affect both the genders, but girls have a slight predominance.⁴

The exact aetiology of JDM is not clearly understood. Evidence suggests the interplay between environmental triggers, immune dysfunction and specific tissue responses in genetically susceptible individuals. In JDM, vasculopathy is the common underlying pathology observed in all damaged tissues. It primarily affects skin and muscles but can also involve other organs such as lungs, heart and central nervous system.⁵ Besides the hallmark features, children often have low-grade fever, malaise, weight loss and poor appetite.

A study of 175 children with JDM from the UK revealed presence of characteristic rash or Gottron’s in 88%, proximal muscle weakness in 82%, systemic features in 81%, elevated muscle enzymes in 80% and abnormal MRI in 76%. Of the muscle enzymes, CPK was elevated in 64%, LDH in 74% and ALT/AST in 48%.⁶ The unusual manifestations in our patient include a subtle presentation of proximal muscle weakness with normal muscle enzymes, absence of the characteristic cutaneous features which probably led to delay in diagnosis, which in turn contributed to the development of calcinosis. MRI of thighs and muscle biopsy were useful in this scenario to help make the diagnosis.

Calcinosis in JDM is generally associated with delay to diagnosis, a longer duration of untreated active disease, inadequate treatment, underlying cardiac or pulmonary disease and may involve skin, subcutaneous tissue, myofascial plane and muscles.⁷ Calcinosis cutis appears as hard, nodular swelling over the skin or subcutaneous areas of the body. This may lead to severe complications like ulceration of skin, secondary infections, contractures, functional disability and nerve entrapment.

Calcinosis usually occurs as a result of dystrophic calcification, the underlying pathogenesis of which is still unclear. Release of calcium from mitochondria of muscle cells has been cited as a possible cause. Macrophages, proinflammatory cytokines and impairment of calcium regulating proteins have been implicated.⁸

As far as long-term outcome is concerned about 41% have a moncyclic course and 59% have a chronic/polycyclic course. Persistent disease activity occurs in up to 60% of patients, 69% patients suffer from cumulative damage and 6.5% have major impairment.⁹

Nephrocalcinosis on the other hand is a pattern of renal injury characterised by deposition of excessive calcium in renal tubules and interstitium. Individuals may be asymptomatic or may present with symptoms related to the condition causing nephrocalcinosis. If kidney stones are present, symptoms may include flank pain, dysuria, haematuria and passage of mud-like material or stones in urine.¹⁰ The spectrum of renal involvement in adults with dermatomyositis includes acute kidney injury, chronic kidney disease, myoglobinuria, haematuria, proteinuria and hypertension. Data on renal involvement in children with inflammatory myopathy are scarce. Though our patient had bilateral nephrocalcinosis, he did not present with any of the above manifestations. Investigations to look for other potential causes of nephrocalcinosis were also normal.

Early recognition of disease pattern and aggressive management of patients with steroids and disease modifying agents can improve the prognosis in JDM. In children with disease-associated calcinosis, in addition to steroids and immunomodulatory therapy, alternative agents such as bisphosphonates, calcium channel blockers, sodium thiosulphate, probenicid and aluminium hydroxide have been used for treatment of calcinosis. Apart from steroids and disease modifying agents, biologics such as rituximab, abatacept and anti-TNF agents like infliximab and adalimumab have also been found to be useful.^{11 12} We did not use biologics in our patient because they could not afford the cost of biologic therapy. The outcome has not been consistent with any of these individual drugs or as a combination therapy.¹³

Patient’s perspective.

My child was a happy boy, always active and energetic until 7 months ago, when one day, on returning from school complained of pain around his elbows. I had a look at it and noticed small mosquito bite like rashes. I applied some cream over the elbows and didn’t worry too much about it. Slowly over the next 6 months or so he started getting painful lumps on his forearms and legs which made me worried. My family doctor examined my child and referred us to a paediatric rheumatologist. He examined my child and ordered blood tests, scans and a biopsy from his thigh muscle. The diagnosis of a rare muscle disorder was made. The doctor explained that the painful lumps my child had, was due to calcium deposits under the skin and this could have been due to long term untreated disease and that my child could have had inflammation in his muscles long before the lumps started appearing. Thinking back, I now feel that my boy’s energy levels had dropped recently compared with last year and he was taking longer to climb stairs. I had mistakenly attributed this to laziness. The doctor also said that the ultrasound report showed calcium deposits in his kidneys and referred us to a nephrologist. The nephrologist went through his ultrasound reports and ordered a few more blood and urine tests. She explained to us that the calcium in his kidneys were likely due to the muscle disease and gave him a few more medications for kidney stones. At present, my child is doing well. I have noticed he is more energetic these days and the painful lumps have reduced in size with treatment. I feel privileged to write this perspective about my child’s health, and I hope this experience will help parents and other physicians gain knowledge about this condition.

Learning points.

• The initial presentation of juvenile dermatomyositis (JDM) may be subtle without characteristic cutaneous features or elevated muscle enzymes.

• Extensive calcinosis may be the presenting feature of JDM when the disease is missed in early stages.

• A muscle biopsy must be performed when classical clinical features are absent.

• Prompt diagnosis of JDM and aggressive therapy is required to reduce long-term morbidity.

• Nephrocalcinosis though rare may be found in association with JDM related calcinosis.