Calcinosis universalis complicating juvenile dermatomyositis: Improvement after intravenous immunoglobulin therapy

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108 Letters to the editor / Joint Bone Spine 80 (2013) 104–114

Ilaria Puxeddu

^a

Francesca Bongiorni

^a

Daniele Chimenti

^a

Riccardo Capecchi

^a

Stefano Bombardieri

^b

Alessandro Moretta

^c

Cristina Bottino

^c^,^d

Paola Migliorini

^a,∗

a

Clinical Immunology, Department of Internal Medicine, University of Pisa, via Roma 67, 56126 Pisa, Italy

b

Rheumatology Units, Department of Internal Medicine, University of Pisa, 56126 Pisa, Italy

c

Department of Experimental Medicine, University of Genova, Genova, Italy

d

G. Gaslini Institute, Genova, Italy

∗

Corresponding author. Tel.: +39 50 55 86 28;

fax: +39 50 55 86 30.

E-mail address: paola.migliorini@med.unipi.it (P. Migliorini) Accepted 23 May 2012 Available online29 December 2012

doi:10.1016/j.jbspin.2012.05.002

Calcinosis universalis complicating juvenile dermatomyositis:

Improvement after intravenous immunoglobulin therapy

a r t i c l e i n f o

Keywords:

Calcinosis universalis Intravenous immunoglobulin Juvenile dermatomyositis

1. Introduction

Calcinosis universalis is a rare and incapacitating complica- tion of juvenile dermatomyositis. No speciﬁc treatment exists and not all cases respond to available treatments. We report the case of a young man with juvenile dermatomyositis and incapacitat- ing refractory calcinosis universalis that resolved after intravenous immunoglobulin therapy.

2. Case report

This male patient was diagnosed at 10 years of age with juve- nile dermatomyositis manifesting as inflammatory polyarthralgia, myalgia, severe muscle fatigability, heliotrope eyelid edema, and Gottron’s papules. High levels were found for muscle enzymes, particularly creatinine phosphokinase (CPK). Electromyography findings suggested a myogenic process and a muscle biopsy showed signs of inflammatory muscle disease. Low-dose glucocorticoid therapy and methotrexate were given.

Calcinosis universalis developed. Treatments included 20 pamidronate bolus injections, cyclosporine (1 year), diltiazem (7 months), alendronate (1 year), probenecid (6 months), and colchicine. None of these drugs was effective. Sinus tracts devel- oped at the calciﬁcation sites, leading to infections.

Intravenous immunoglobulin therapy was started in a dosage of 2 g/kg/month. The calciﬁcations were marked and photographed, and standard radiographs were obtained before and after intra-

Fig. 1.Anteroposterior pelvic radiographs (A) before and (B) after intravenous immunoglobulin therapy (IVIg): note the shrinkage of the calciﬁcations.

venous immunoglobulin therapy. Laboratory tests were normal.

After the fourth injection, the patient reported alleviation of the myalgia and muscle fatigability, which prompted tapering of the glucocorticoid dosage. No new calcifications were detected and, even more importantly, no new sinus tracts developed. The clinical (Supplementary data, Fig. S1) and radiographic (Fig. 1) evaluations indicated marked regression of the calcifications, most notably at the sacrum and knees, with resolution of the knee flexion contrac- ture and limp. The efficacy of intravenous immunoglobulin therapy was sustained at last follow-up 7 years later.

3. Discussion

Intravenous immunoglobulin therapy has been proven effec- tive in dermatomyositis, most notably in patients with resistance to glucocorticoid therapy [1–4]. However, the only data sug- gesting beneﬁts in calcinosis universalis come from anecdotal case-reports. Yang et al. reported regression of the calciﬁcations during intravenous immunoglobulin therapy in a 10-year-old boy with calcinosis universalis [5]. Slimani et al. described complete resolution of calcinosis universalis complicating juvenile dermato- myositis in a 14-year-old girl after 2 years of pamidronate therapy (2 mg/kg/year) [6].

In our patient, the calcinosis universalis failed to respond to a broad array of drugs. After the initiation of intravenous immunoglobulin therapy, no new sinus tracts developed. Fur- thermore, the beneﬁcial effects allowed glucocorticoid treatment tapering after only four infusions. The clinical and radiographic data collected at baseline and after 9 months of treatment showed shrinkage of the calciﬁcations.

Nevertheless, in addition to speciﬁc effects of intravenous immunoglobulin therapy, spontaneous resolution of the calcinosis universalis cannot be ruled out. Furthermore, we cannot exclude a role for the numerous drugs taken previously, particularly the pamidronate.

In sum, our case-report suggests that intravenous immunoglob- ulin therapy may be effective in calcinosis universalis refractory to the other treatments advocated in the literature.

Disclosure of interest

The authors declare that they have no conﬂicts of interest con- cerning this article.

Appendix A. Supplementary data

Supplementary data (Fig. S1) associated with this article can be

found, in the online version, at http://www.sciencedirect.com, at

doi:10.1016/j.jbspin.2012.07.001.

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Letters to the editor / Joint Bone Spine 80 (2013) 104–114 109

References

[1] Al-Mayouf SM, Laxer RM, Schneider E, et al. Intravenous immunoglobulin therapy for juvenile dermatomyositis: efﬁcacy and safety. J Rheumatol 2000;27:2498–503.

[2] Cherin P, Herson S, Wechsler B, et al. Efﬁcacy of intravenous immunoglobulin therapy in chronic refractory polymyositis and dermatomyositis: an open study with 20 adult patients. Arthritis Rheum 1991;91:162–8.

[3] Lang BA, Laxer RM, Murphy G, et al. Treatment of dermatomyositis with intravenous gammaglobulin. Am J Med 1991;91:169–72.

[4] Vedanarayanan V, Subramony SH, Ray LI, et al. Treatment of childhood dermatomyositis with high dose intravenous immunoglobulin. Pediatr Neurol 1995;13:336–9.

[5] Yang MC. Improvement of juvenile dermatomyositis with calcinosis universalis after treatment with intravenous immunoglobulin. Int J Rheum Dis 2008;11:77–80.

[6] Slimani S, Abdessemed A, Haddouche A, et al. Complete resolution of universal calcinosis in a patient with juvenile dermatomyositis using pamidronate. Joint Bone Spine 2010;77:70–2.

Meriem Touimy

^∗

Saadia Janani Wafae Rachidi Nouﬁssa Etaouil Ouafa Mkinsi Service de rhumatologie, CHU Ibn-Rochd, 1, rue des hôpitaux, Casablanca, Morocco

∗

Corresponding author. 38, rue Ibn-Toumert, CP 20490, Casablanca, Morocco.

Tel.: +212 669 716 041.

E-mail address: mtouimy@gmail.com (M. Touimy) Accepted 7 June 2012 Available online19 September 2012

doi:10.1016/j.jbspin.2012.07.001

Macrophage activation syndrome revealing disseminated tuberculosis in a patient on inﬂiximab

a r t i c l e i n f o

Keywords:

TNF-alpha antagonists Tuberculosis

Macrophage activation syndrome

A 73-year-old male with active psoriatic arthritis despite leflunomide (20 mg/day) and prednisone (5 mg/day) was evaluated for TNF- ␣ antagonist therapy. The chest radiograph was normal and the intradermal tuberculin test and Quantiferon TB Gold test were negative. Infliximab therapy was started. Two weeks after the third infliximab infusion, he was admitted for a fever with a decline in general health. The physical examination showed weight loss with no focal abnormalities. Laboratory tests showed C-reactive pro- tein elevation to 286 mg/L; increases in serum liver transaminase levels (8N), ferritin (40N), triglycerides (3N), and lactic dehydro- genase (10 N); gradually worsening pancytopenia (hemoglobin, 9.9 g/dL; leukocytes, 1430/mm

³

; and platelets, 20,000/mm

³

); and a decrease in serum ﬁbrinogen to 1.70 g/L. Computed tomography of the chest, abdomen, and pelvis visualized tiny linear densities in the lung apices, suggesting sequellar changes, with no parenchymatous densities. Micronodules were visible in the spleen. Results were negative from microbiological studies of a variety of specimens.

The intradermal tuberculin test was negative and the Quantiferon TB Gold indeterminate. A bone marrow biopsy showed T-cell inﬁl- tration, an epithelioid granulomatous reaction, and hemophagocy- tosis (Figs. 1 and 2); the acid-fast stain was negative. The patient

Fig. 1.Giant cell granuloma. HES stain×400.

died of multiorgan failure 10 days after his admission. Two days later, the bone marrow and endotracheal specimens collected in the intensive care unit were found to be positive for Mycobacterium tuberculosis.

The incidence of tuberculosis during TNF- ␣ antagonist ther- apy has been evaluated in France at 116.7/100,000 patient-years [1] and is higher with the monoclonal antibodies [2]. A high rate of extrapulmonary lesions (>50%) and disseminated involvement raises diagnostic challenges [1,2]. Thus, in 10% of cases, the diag- nosis must rely on a clinical suspicion and a favorable response to a treatment trial [1]. Our case indicates that microbiologi- cal specimens should be collected routinely and repeatedly in patients with unexplained fever during TNF- ␣ antagonist ther- apy. An epithelioid granuloma or caseous necrosis suggests the diagnosis. Tuberculosis during TNF- ␣ antagonist therapy is usually due to reactivation of preexisting latent tuberculosis, explaining the short time from treatment initiation to symptom onset [1,2].

Although the pretreatment workup showed no evidence of tuber- culosis in our patient, reactivation was the most likely mechanism.

Fig. 2.Immunohistochemistry study with the macrophage label anti-CD68 antibody×630. Labeled macrophage cytoplasm is brown and contains unla- beled erythrocytes. The macrophage nucleus is displaced peripherally, and the erythrocyte-laden cytoplasm resembles a bag of marbles.