Tab Application Banner
  • Users Online: 641
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
Year : 2020  |  Volume : 15  |  Issue : 6  |  Page : 205-208

Tacrolimus in refractory juvenile dermatomyositis: Case report and review of literature

1 Pediatric Rheumatology Clinic, Indira Gandhi Institute of Child Health and Manipal Hospital, Bengaluru, Karnataka, India
2 Department of Pediatrics, Indira Gandhi Institute of Child Health, Bengaluru, Karnataka, India
3 Pediatric Rheumatology Clinic, Indira Gandhi Institute of Child Health and Columbia Asia Hospital, Bengaluru, Karnataka, India

Date of Submission18-May-2020
Date of Acceptance29-Jun-2020
Date of Web Publication18-Jan-2021

Correspondence Address:
Dr. Anand Prahalad Rao
Vijaya Children's Clinic, #162/A, Arekere Mico Layout, Bannerghatta Road, Bengaluru - 560 076, Karnataka
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/injr.injr_128_20

Rights and Permissions

Juvenile dermatomyositis (JDM) is the most common type of inflammatory myositis in childhood, characterized by proximal muscle weakness and rash. The standard treatment of JDM involves steroids and methotrexate (MTX). A small proportion of patients do not respond to steroids and MTX. We present a couple of patients with refractory JDM who had failed to respond to steroids and MTX. Introduction of tacrolimus led to complete remission of the disease in a patient and partial control in the other. Literature review was done which revealed ten patients with JDM who were treated with tacrolimus with encouraging results in the form of significant reduction in the cutaneous and muscle disease activity. Tacrolimus is an useful drug in the management of refractory JDM.

Keywords: Juvenile dermatomyositis, methotrexate tacrolimus, refractory

How to cite this article:
Rao AP, Kolli V, Rajarathinam I, Raghuram J. Tacrolimus in refractory juvenile dermatomyositis: Case report and review of literature. Indian J Rheumatol 2020;15:205-8

How to cite this URL:
Rao AP, Kolli V, Rajarathinam I, Raghuram J. Tacrolimus in refractory juvenile dermatomyositis: Case report and review of literature. Indian J Rheumatol [serial online] 2020 [cited 2022 Dec 10];15:205-8. Available from:

  Introduction Top

Juvenile dermatomyositis (JDM) is the most common form of inflammatory myositis in children. The classical manifestations include symmetrical, proximal muscle weakness along with cutaneous manifestations such as Gottron's papules and heliotrope rash.[1] The incidence of this condition is 3.2 cases per million children per year.[2] The mainstay of treatment for JDM remains daily oral corticosteroid therapy along with methotrexate (MTX). Patients refractory to this regimen are usually treated with intravenous immunoglobulin (IVIG), cyclophosphamide, cyclosporine A, hydroxychloroquine, mycophenolate mofetil (MMF), rituximab, and tumor necrosis factor-alpha antagonists. However, many of the drugs mentioned are either expensive or are associated with significant immunosuppression. Cyclosporine, a calcineurin inhibitor, selectively suppresses T lymphocytes. It has been found to be a very useful drug in the management of refractory JDM.[3] Oral cyclosporine has a disadvantage of erratic absorption and rapid metabolism leading to difficulties in the clinical management of patients.[4] Tacrolimus belongs to calcineurin inhibitor group and has better efficacy as compared to cyclosporine. We present our experience of two children with refractory JDM who were treated with oral tacrolimus. Informed consent was taken from the attendants of both the patients for publication of the case report.

  Case Reports Top

Case 1

An 11-year-old boy was diagnosed as having JDM based on proximal muscle weakness with heliotrope rash along with elevated muscle enzymes and magnetc resonance imaging features of myosits as can be seen in [Figure 1] and [Figure 2]. He was treated with intravenous pulse methylprednisolone (30 mg/kg/dose) for 3 days followed by oral prednisolone 1 mg/kg/day along with MTX at 15 mg/m2/week. In spite of being on 1 mg/kg/day of oral steroids for a period of 4 weeks along with parenteral MTX, there was worsening with recurrent fever spikes, persistent muscle weakness with Childhood Myositis Assessment Scale (CMAS) being 22/52, hypoalbuminemia, and anasarca along with severe abdominal pain, which suggested a possible gastrointestinal vasculitis. Tacrolimus was added on, and improvement was noted in the first 4 weeks of treatment with resolution of edema, improvement in muscle power, and improvement in truncal and neck flexor weakness. Steroids could be tapered and stopped within 7 months of initiation of tacrolimus. CMAS improved to 52/52 within 11 months after the initiation of treatment and tacrolimus was tapered and stopped. Subsequently, MTX was also tapered and stopped after a year in remission off steroids.
Figure 1: Heliotrope rash in the first patient

Click here to view
Figure 2: MRI of the thighs of both patients showing T2 hyperintensities suggesting Inflammatory myositis

Click here to view

Case 2

An 8-year-old boy was diagnosed with JDM with a 2-month history of fever, proximal muscle weakness, and vasculitic rashes over the extremities with arthritis. On examination, Gottron's papules and heliotrope rash were present. The hybrid Manual Muscle Testing 8 (MMT8)/CMAS score was used in this patient, which has been subsequently validated, and the score was 31 out of a total of 100. Serum muscle enzyme levels were elevated. The patient was treated initially with methylprednisolone pulse therapy, followed by oral prednisone 1 mg/kg/day and MTX at 15 mg/m2 once a week. Due to persistent skin and muscle disease activity after 2 months of initiation of therapy with hybrid MMT8/CMAS score of 30/100, MMF at 600 mg/m2/dose in twice-daily dose was added. The child continued to be on methyl prednisolone pulses at 30 mg/kg for 3 days every month and oral prednisolone at 1 mg/kg/day along with MTX and MMF. In view of persistent cutaneous disease activity and persistent myositis with hybrid MMT8/CMAS score of 45/100 after 2 months of initiation of MMF (after 4 months of diagnosis and initiation of therapy), tacrolimus was added at the dose of 0.1 mg/kg/day in two divided doses. The patient started showing improvement within the first few months of the initiation of therapy (hybrid MMT8/CMAS score of 61/100 at 3 months post initiation of therapy with tacrolimus) and steroid dose reduced from 1 to 0.5 mg/kg/day with disappearance of cutaneous disease activity. At the last follow-up, 18 months after the initiation of tacrolimus, hybrid MMT8/CMAS score was 70/100 without any evidence of cutaneous disease activity, and the patient was on 0.4 mg/kg of oral prednisolone and stable doses of MMF and MTX. In both the cases, the monitoring of possible adverse events of tacrolimus was done by periodic urine examination, serum creatinine estimation, and blood pressure monitoring.

  Discussion Top

This case series highlights the usefulness of tacrolimus in patients with refractory JDM. Tacrolimus is a calcineurin inhibitor, which inhibits interleukin-2-driven T cell activation. It has proven to be of use in many rheumatological diseases including systemic lupus erythematosus (lupus nephritis), adult polymyositis, and dermatomyositis. There have been multiple case reports of the use of tacrolimus in refractory JDM.[5],[6],[7] Both the children in the current series had severe muscle weakness and skin disease at the time of diagnosis. The disease was refractory to corticosteroids and MTX. Yamada et al. reported the successful use of oral tacrolimus in a 13-year-old patient with refractory JDM who had not responded to MTX, steroids, Azathioprine (AZA), IVIg, and oral cyclosporine A as can be seen in [Table 1].[5] Nalda et al. conducted a retrospective analysis of six patients who had a refractory JDM and who were treated for a period of 12 months with oral tacrolimus.[6] They reported a significant improvement in both cutaneous and muscle disease in all these patients, and no significant tacrolimus-related adverse events were reported in any of these patients. Hassan et al. reported three cases with refractory JDM with severe skin vasculitis and significant muscle weakness, who responded to tacrolimus in the form of improvement in skin lesion and myositis but did not see any improvement of muscle strength.[7] Our results were consistent with those of previous case reports in the literature, which showed significant improvement in muscle strength and skin lesions with tacrolimus.[5],[6],[7] In the present case report, we observed improvement in muscle strength and cutaneous manifestations in both patients after the incorporation of tacrolimus into the treatment regimen. It was possible to reduce steroids and stop in the first patient (monocyclic course) and in case 2 (persistent disease course), the authors were able to reduce steroid dose (from 1 to 0.4 mg/kg/day). These results suggest that additional use of tacrolimus led to a reduction of the daily dose of steroids without significant worsening of clinical symptoms and laboratory data. Davies et al. reported that tacrolimus increases the affinity of the glucocorticoid receptor to corticosteroid and also increases the intracellular concentration of steroid by blocking its export from the cell.[8] Tacrolimus sometimes causes various adverse effects such as renal dysfunction, gastrointestinal symptoms, hypertension, nephrotoxicity, neurotoxicity, impaired glucose metabolism, hyperkalemia, tremor, headache, and sleeping disorders.[9] No adverse effects of tacrolimus were observed in our patients. Findings from previous case reports showed tacrolimus to be safe after a follow-up period of 1–2 years.[5],[6],[7]
Table 1: Clinical profile of refractory juvenile dermatomyositis patients treated with tacrolimus

Click here to view

  Conclusion Top

Tacrolimus is an effective immunomodulatory agent in the management of refractory JDM. Tacrolimus introduction led to a significant reduction of disease activity with reduction in the requirement of oral prednisolone to control the disease. This case report highlights the fact that when tacrolimus administered in an early phase can improve both cutaneous manifestations and muscle weakness in refractory JDM. However, the authors admit that this being a very small patient series, generalization might not be in order, and it must be stressed that larger clinical trial with this drug might lead to more robust data for the proof of its usefulness.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given his consent for images and other clinical information to be reported in the journal. The guardian understands that names and initials will not be published, and due efforts will be made to conceal patient identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Feldman BM, Rider LG, Reed AM, Pachman LM. Juvenile dermatomyositis and other idiopathic inflammatory myopathies of childhood. Lancet 2008;371:2201-12.  Back to cited text no. 1
Mendez EP, Lipton R, Ramsey-Goldman R, Roettcher P, Bowyer S, Dyer A, et al. US incidence of juvenile dermatomyositis, 1995–1998: Results from the National Institute of Arthritis and Musculoskeletal and Skin Diseases Registry. Arthritis Care Res 2003;49:300-5.  Back to cited text no. 2
Heckmatt J, Saunders C, Peters AM, Rose M, Hasson N, Thompson N, et al. Cyclosporin in juvenile dermatomyositis. Lancet 1989;333:1063-6.  Back to cited text no. 3
Holt DW, Johnston A, Roberts NB, Tredger JM, Trull AK. Methodological and clinical aspects of cyclosporin monitoring: Report of the Association of Clinical Biochemists task force. Ann Clin Biochem 1994;31:420-46.  Back to cited text no. 4
Yamada A, Ohshima Y, Omata N, Yasutomi M, Mayumi M. Steroid-sparing effect of tacrolimus in a patient with juvenile dermatomyositis presenting poor bioavailability of cyclosporine A. Eur J Pediatr 2004;163:561-2.  Back to cited text no. 5
Nalda AM, Caballero CM, Guimeral CA, Rom MB, Garcia PB. Efficacy of tacrolimus (FK-506) in the treatment of recalcitrant juvenile dermatomyositis: Study of 6 cases. Med Clin 2006;127:697-701.  Back to cited text no. 6
Hassan J, van der Net JJ, van Royen-Kerkhof A. Treatment of refractory juvenile dermatomyositis with tacrolimus. Clin Rheumatol 2008;27:1469-71.  Back to cited text no. 7
Davies TH, Ning YM, Sanchez ER. Differential control of glucocorticoid receptor hormone-binding function by tetratrico- peptide repeat (TPR) proteins and the immunosuppressive ligand FK506. Biochemistry 2005;44:2030-8.  Back to cited text no. 8
Wallemacq PE, Verbeeck RK. Comparative clinical pharmacokinetics of tacrolimus in paediatric and adult patients. Clin Pharmacokinet 2001;40:283-95.  Back to cited text no. 9


  [Figure 1], [Figure 2]

  [Table 1]

This article has been cited by
1 Methotrexate/methylprednisolone/prednisolone
Reactions Weekly. 2021; 1855(1): 219
[Pubmed] | [DOI]


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  In this article
Case Reports
Article Figures
Article Tables

 Article Access Statistics
    PDF Downloaded208    
    Comments [Add]    
    Cited by others 1    

Recommend this journal