GAMMA-carboxyglutamate excretion and calcinosis in juvenile dermatomyositis

Proteins containing gamma-carboxyglutamic acid (Gla) are present in subcutaneous calcifications of adults with dermatomyositis or scleroderma. Sixteen children with juvenile dermatomyositis, including 7 with subcutaneous calcifications, were studied to determine if abnormal synthesis or turnover of Gla-containing proteins occurred. All study children had increased excretion of the amino acid that was greater than that of age-and sex-matched controls. Patients who had juvenile dermatomyositis with calcifications had a 3-fold increase in Gla excretion, and those without calcinosis had a 2-fold increase. Five other children with various connective tissue disorders and subcutaneous calcification had 2-fold increased Gla excretion. Decreased excretion of this amino acid was associated with salicylate therapy (80 mg/kg/24 hours). The data suggest an abnormal turnover of Gla-containing proteins in juvenile dermatomyositis. Metabolism of these proteins may be involved in the pathophysiology of soft-tissue calcification in children.     

Bisphosphonates in juvenile dermatomyositis with dystrophic calcinosis

Abstract

Objectives. Our primary objective was to retrospectively analyze whether bisphosphonates initiated in combination with immunosuppressive drugs and/or intravenous immunoglobulin (IVIG) resulted in a radiological and clinical improvement of dystrophic calcinosis in six female juvenile dermatomyositis (JDM) patients.

Methods. Medical records of the patients were reviewed. All six patients met the Bohan and Peter diagnostic criteria for JDM.

Results. A resolution of calcinosis was observed in four of the six patients with JDM following the use of bisphosphonates and intensive immunosuppressive therapy with or without IVIG. Bisphosphonates were unable to either decelerate the progression of calcinosis or improve calcinosis in cases 5 and 6. In case 5, it took a relatively long time to control the disease activity despite the appropriate immunsuppressive treatment and she experienced multiple flares of active JDM. Case 6 had a long duration of severe active disease before treatment initiation. No important adverse event was observed.

Conclusions. Early commencement of aggressive immunosuppressive agents in combination with bisphosphonate is a choice for the treatment of calcinosis in JDM patients. Concomitant use of IVIG may have an additional effect on the resolution of calcinosis.     

Hyperimmunoglobulin E syndrome with juvenile dermatomyositis and calcinosis

Juvenile dermatomyositis (JDM) is a rare childhood disease with autoimmune association. Environmental factors are known to trigger JDM in genetically susceptible individuals (Schmieder et al., Dermatol Online 6:3, 2009). Calcinosis is a well-established complication of JDM. Prevalence is higher in children (30–70%; Özkaya et al., Erciyes Med J 30(1):40–43, 2008). Hyperimmunoglobulin E syndrome is a primary immunodeficiency syndrome with multiple recurrent abscess formation and raised serum immunoglobulin E levels. We report a case of JDM with calcinosis cutis universalis with hyperimmunoglobulin E syndrome. With a previous similar case report (Min et al., Korean J Intern Med 14:95–98, 1999), this could well be a new sequence syndrome where abscesses are the trigger for the onset of JDM.     

Hyperimmunoglobulin E syndrome with juvenile dermatomyositis and calcinosis

Juvenile dermatomyositis (JDM) is a rare childhood disease with autoimmune association. Environmental factors are known to trigger JDM in genetically susceptible individuals (Schmieder et al., Dermatol Online 6:3, 2009). Calcinosis is a well-established complication of JDM. Prevalence is higher in children (30–70%; Özkaya et al., Erciyes Med J 30(1):40–43, 2008). Hyperimmunoglobulin E syndrome is a primary immunodeficiency syndrome with multiple recurrent abscess formation and raised serum immunoglobulin E levels. We report a case of JDM with calcinosis cutis universalis with hyperimmunoglobulin E syndrome. With a previous similar case report (Min et al., Korean J Intern Med 14:95–98, 1999), this could well be a new sequence syndrome where abscesses are the trigger for the onset of JDM.

     

Using imaging methods to assess severe calcinosis in juvenile dermatomyositis: A case report

Calcinosis and lipodystrophy are severe complications of juvenile dermatomyositis (JDM). Up to 20% of patients have calcinosis, and the onset of calcinosis usually occurs 1 to 3 years after that of the illness. We report a case of JDM with severe complications of calcinosis and lipodystrophy, and we assess calcinosis using a variety of imaging methods. To evaluate the patient's inflammatory state, bone scintigraphy was performed, which demonstrated increased uptake in the right scapula, in addition, multiple calcifications are present subcutaneously on the shoulder and back, and inflammatory imaging features are also present in the right knee joint.     

Multi-center analysis of calcinosis in children with juvenile dermatomyositis]

OBJECTIVES: To reveal the frequency and the clinical characteristics of dystrophic calcification that occurs in children with juvenile dermatomyositis, multi-center analysis was constructed. METHOD: Fifty children with JDM were enrolled, and 14 of them (28.0%) were complicated with calcinosis. Clinical symptoms and laboratory tests at onset, initial therapy and disease course were compared in children with and without calcinosis. RESULTS: The mean age of the onset of calcinosis was 4.78 +/- 3.33 years, and it was younger than those of children without calcinosis (8.66 +/- 3.85 years) (P = 0.0017). No differences of clinical manifestation except Gower's sign were observed. The frequency of positive anti-nuclear antibody was 7.1% in children with calcinosis and 52.9% without calcinosis (P = 0.0112). The initial therapy of methylprednisolon pulses gave no effects on prognosis of calcium deposition. The calcinosis appeared in 1.56 +/- 1.91 year after the onset of the disease. The various types of calcium deposition including large tumorous clumps, subcutaneous plaques or nodules, sheet-type calcification were deserved. They appeared over knee joints (64.3%), elbow joint (64.3%), and hip processes (50.0%). Calcinosis affecting the subcutaneous tissues frequently resulted in painful superficial ulceration of the overlying skin (42.9%), local infection (50.0%), and limitation of joint movement (14.3%). Although aluminum phosphate was effective in 2 children among 7, no other effective treatment was recommended. In 5 cases, surgical removal of tumorous clumps was operated. Thus, juvenile dermatomyositis is frequently complicated with calcinosis. This type of calcinosis was found to be unlikely to resolve completely, and resulted in severe disability in children.     

Rapid improvement of calcinosis in juvenile dermatomyositis with alendronate therapy

A 6-year-old boy with improving juvenile dermatomyositis (JDM) developed severe and debilitating calcinosis, unresponsive to diltiazem and probenecid. Alendronate produced dramatic improvement within 1 month and by 12 months calcinosis had virtually resolved. The response was followed by bone mineral content measurements.     

Hypercalcemia during the resolution of calcinosis universalis in juvenile dermatomyositis.

Dystrophic calcification is seen in more than 50% of children with juvenile dermatomyositis and tends to resolve spontaneously in some patients. Calcinosis universalis is the least common type of calcification seen and rarely regresses. We describe a boy with juvenile dermatomyositis and calcinosis universalis who developed hypercalcemia during spontaneous regression of dystrophic calcification. The treatment and possible mechanisms of this complication are discussed.     

Improvement of juvenile dermatomyositis with calcinosis universalis after treatment with intravenous immunoglobulin

Juvenile dermatomyositis is a chronic multisystemic disease. It is believed to be of autoimmune aetiology and is characterized by the presence of vasculitis affecting striated muscle and skin. Calcinosis occurs in about 40% of cases. We report a case of a 10‐year‐old girl diagnosed with juvenile dermatomyositis who presented with difficulty in walking and inability to completely extend the four extremities due to calcinosis universalis. Calcinosis had progressed despite a 3‐year administration of diltiazem, hydroxychloroquine, aluminium hydroxide, cyclosporin, and probenecid. The introduction of monthly intravenous immunoglobulin therapy for 15 months lessened disease activity, and markedly regressed calcinosis, and improved functional outcome.     

Treatment of Achilles tendon calcinosis in juvenile dermatomyositis with external ilizarov fixator

Calcinosis is a devastating complication of juvenile dermatomyositis and a challenging therapeutic problem. We report the use of an external Ilizarov fixator for the treatment of Achilles tendon calcinosis causing severe disability in a young girl with juvenile dermatomyositis.     

Efficacy of probenecid for a patient with juvenile dermatomyositis complicated with calcinosis

Calcinosis of juvenile dermatomyositis (JDM) is a crucial problem because it is refractory to various therapies. An 11-year-old boy who had been treated for JDM with interstitial pneumonia developed calcinosis of both legs despite treatment with corticosteroid and cyclosporin A. Images of his knees showed massive calcinosis with restricted range of motion. Probenecid was used to reduce calcinosis, resulting in remarkable improvement of calcinosis accompanied by normalization of serum phosphorus level and disability after 17 months of administration. We suggest that probenecid is useful for the treatment of calcinosis of JDM.     

Pulmonary infarction complicating thrombophlebitis of the upper extremity

Five cases of thrombophlebitis of the upper extremity in which pulmonary embolism occurred as a complication are presented. The etiology was secondary to chemical irritation in two cases, was unknown in one case and was probably traumatic in the fifth case. All of the patients having pulmonary emboli received anticoagulant therapy. Pulmonary emboli were controlled satisfactorily in two of the five patients. One patient died from repeated pulmonary emboli originating in the right axillary, brachial and subclavian veins, and multiple pulmonary infarctions were demonstrated at postmortem examination. Venous ligation was necessary in one of the remaining cases, and the fifth patient continued to have hemoptysis for six weeks even though the prothrombin time was maintained at therapeutic levels. This patient subsequently had recurrent thrombophlebitis of the upper extremity with pulmonary embolism, from which he recovered with conservative therapy.     

Autoantibodies to a 140‐kd protein in juvenile dermatomyositis are associated with calcinosis

Objective

The identification of novel autoantibodies in juvenile dermatomyositis (DM) may have etiologic and clinical implications. The aim of this study was to describe autoantibodies to a 140‐kd protein in children recruited to the Juvenile DM National Registry and Repository for UK and Ireland.

Methods

Clinical data and sera were collected from children with juvenile myositis. Sera that recognized a 140‐kd protein by immunoprecipitation were identified. The identity of the p140 autoantigen was investigated by immunoprecipitation/immunodepletion, using commercial monoclonal antibodies to NXP‐2, reference anti‐p140, and anti‐p155/140, the other autoantibody recently described in juvenile DM. DNA samples from 100 Caucasian children with myositis were genotyped for HLA class II haplotype associations and compared with those from 864 randomly selected UK Caucasian control subjects.

Results

Sera from 37 (23%) of 162 patients with juvenile myositis were positive for anti‐p140 autoantibodies, which were detected exclusively in patients with juvenile DM and not in patients with juvenile DM–overlap syndrome or control subjects. No anti‐p140 antibody–positive patients were positive for other recognized autoantibodies. Immunodepletion suggested that the identity of p140 was consistent with NXP‐2 (the previously identified MJ autoantigen). In children with anti‐p140 antibodies, the association with calcinosis was significant compared with the rest of the cohort (corrected P < 0.005, odds ratio 7.0, 95% confidence interval 3.0–16.1). The clinical features of patients with anti‐p140 autoantibodies were different from those of children with anti‐p155/140 autoantibodies. The presence of HLA–DRB1*08 was a possible risk factor for anti‐p140 autoantibody positivity.

Conclusion

This study has established that anti‐p140 autoantibodies represent a major autoantibody subset in juvenile DM. This specificity may identify a further immunogenetic and clinical phenotype within the juvenile myositis spectrum that includes an association with calcinosis.

     

Case report: severe central nervous system involvement in juvenile dermatomyositis

We present 3 patients with juvenile dermatomyositis (JDM) and severe central nervous system (CNS) complications. All patients had at least 4 positive criteria of Bohan and Peter, which confirmed a definite diagnosis of JDM. They were all male, and had a relatively high creatinine kinase value at admission (1532-4260 U/l). Besides, progressive proximal muscle weakness and rash, one patient presented with rapid irreversible decline of vision. Ophthalmologic examination showed active vasculitis of the retina. After 2 weeks of treatment with immunosuppressive drugs and being in improved, relatively stable clinical condition, all 3 patients developed generalized tonic-clonic convulsions. Other causes of the neurological symptoms could be excluded. In all 3 patients, the course of JDM was fatal. The clinical symptoms and further investigations in our patients show CNS involvement in JDM. Although rarely reported, CNS vasculopathy can be a serious and life-threatening complication of JDM.     

Nephrotic syndrome and juvenile dermatomyositis

Juvenile dermatomyositis (JDM) is a rare autoimmune disease characterized by proximal muscle weakness, skin lesions, gastro intestinal, pulmonary, cardiac and small nerve damage. Renal involvement has been rarely reported in JDM. This is the report of a 7-year-old boy presented with nephrotic syndrome (NS) and subsequent renal failure. Clinical manifestations of JDM appeared gradually. Renal manifestations could be considered as a rare initial presentation of JDM.