Journal of Rheumatology and Arthritis Case Report Open Access Macrophage Activation Syndrome in a Girl with Juvenile Dermatomyositis Margarita Ganeva1*, Stefan Stefanov1, Albena Telcharova-Mihaylovska1, Katya Temelkova1, Dimitrina Mihaylova1 and Kalin Lisichki2 1Department of Paediatric Rheumatology, Medical University Sofia, Bulgaria 2Pediatric Clinic, Acibadem City Clinic Tokuda Hospital, Sofia, Bulgaria *Corresponding author: Margarita Ganeva, Department of Paediatric Rheumatology, University Children’s Hospital, Medical University Sofia, Bulgaria, Tel: 00359888626874, E-mail: [email protected] Received Date: March 08, 2021 Accepted Date: April 08, 2021 Published Date: April 10, 2021 Citation: Margarita Ganeva (2021) Macrophage Activation Syndrome in a Girl with Juvenile Dermatomyositis. J Rheumatol Arthritis 1: 1-9. Abstract Background: Macrophage activations syndrome (MAS), a hemophagocytic syndrome, is a complication of rheumatic dis- eases, seen most frequently in children with systemic juvenile idiopathic arthritis. MAS is rarely reported in juvenile derma- tomyositis (JDM). MAS can be triggered by various factors including infection or malignancy. Case Presentation: We report a clinical case of a 9-year-old girl who presented, after sunlight exposure, with proximal muscle weakness, characteristic cutaneous changes including heliotrope discoloration of the eyelids with periorbital edema and Gottron’s papules. Based on the clinical signs, a diagnosis of JDM was suspected. Creatine kinase level was not elevated, though characteristic pattern of muscle involvement was seen on thigh muscles magnetic resonance imaging. The patient also had alopecia, aphtous stomatitis, and subtle arthritis with flexion contractures at the elbows and knees. Furthermore, a fall in the complete blood count was observed (with platelet count of 116 × 109/L). A positive test for herpes simplex virus was detected. In addition, jaundice and hepatosplenomegaly were observed. The laboratory studies revealed hepatitis and hyperferritinemia (ferritin 1502 ng/ml). As a result, a diagnosis of JDM, complicated by MAS was established. Pulse therapy with intravenous methylprednisolone and immunoglobulin was started. Conclusion: MAS is a life-threatening condition and may progress to multiple organ failure. MAS is a rare complication of JDM. Therefore, early recognition and immediate therapeutic intervention are critical for the effective management of MAS. Keywords: Macrophage Activation Syndrome; Juvenile Dermatomyositis; Triggers; Case Report List of abbreviations: ACR: American College of Rheumatology; ALC: Absolute Lymphocyte Count; ALP: Alkaline Phos- phatase; ALT: Alanine Transaminase; ANA: Antinuclear Antibodies; аnti-dsDNA: Anti-Double Stranded DNA; anti-gp210: Anti-Glycoprotein-210; anti-LC-1: Anti- Liver Cytosolic Antigen Type 1; anti-LKM1: Anti–Liver-Kidney Microsomal Type 1; anti-PML: Anti-Promyelocytic Leukemia Protein; anti-RNP: Anti-Ribonucleoprotein; аnti- Scl-70: Anti-Scleroderma-70; anti-SLA/LP: Anti-Soluble Liver Antigen/Liver-Pancreas; аnti-Sm: Anti-Smith; аnti-SS-A: Anti-Sjogren’s Syndrome A; an- ©2021 The Authors. Published by the JScholar under the terms of the Crea- tive Commons Attribution License http://creativecommons.org/licenses/ by/3.0/, which permits unrestricted use, provided the original author and source are credited. JScholar Publishers J Rheumatol Arthritis 2021 | Vol 1: 101 2 ti-SS-B: Anti-Sjogren’s Syndrome B; AST: Aspartate Transaminase; CARRA: Children’s Arthritis And Rheumatology Research Alli- ance; CMV: Cytomegalovirus; CRP: C-reactive protein; EBV: Epstein-Barr Virus; EMG: Electromyography; ESR: Erythrocyte Sed- imentation Rate; EULAR: European League Against Rheumatism; GGT: Gamma-Glutamyl Transferase; HAV: Hepatitis A Virus; HBV: Hepatitis B Virus; HCV: Hepatitis C Virus; HSV: Herpes Simplex Virus; Hb: Hemoglobin; Ig: Immunoglobulin; IL: Interleukin; JDM: Juvenile Dermatomyositis; MAS: Macrophage Activations Syndrome; MRI: Magnetic Resonance Imaging; PRINTO: Paediatric Rheumatology INternational Trials Organisation; sJIA: Systemic Juvenile Idiopathic Arthritis; SLE: Systemic Lupus Erythematosus; UVR: Ultraviolet Radiation; WBC: White Blood Cells Background chair, closer to the sea every day. Yellow discoloration of the skin and abdominal pain appeared afterwards. The child was admit- Juvenile dermatomyositis (JDM) is a multisystem dis- ted to the Pediatric rheumatology department of Medical Uni- ease with characteristic changes involving mainly striated mus- versity of Sofia in September 2015, more than one year after the cles and skin. Macrophage activation syndrome (MAS), a form of disease onset. On admission the patient was febrile (38.8 Co) and secondary hemophagocytic lymphohistiocytosis, is a life-threat- appeared ill, cachectic and jaundiced. On examination marked ening complication of rheumatic diseases in children, most com- symmetrical proximal muscle weakness with pain on palpation monly of systemic juvenile idiopathic arthritis [1,13]. MAS has upon squeezing of the proximal muscles was observed. The girl been rarely reported in JDM [2-15]. We report a clinical case of a was unable to perform the usual daily activities on her own (get- 9-year-old girl with JDM complicated with MAS. ting in and out of bed, getting dressed, showering, brushing her teeth, combing her hair). Characteristic cutaneous changes were Case Report observed with heliotrope discoloration of the eyelids with peri- The girl presented in July 2014 with abnormal gait and orbital edema and a malar rash (Figure 1). foot pain which appeared mainly in the evening and after phys- Furthermore, Gottron’s papules over the metacarpo- ical activities. At that time the parents associated the symptoms phalangeal and interphalangeal joints were noticed (Figure 2). with uncomfortable shoes. Six months later the girl was admitted to a Pediatric Department. On examination she had polyarthri- Skin ulcerations over the heel and the elbow were ob- tis, maculopapular rash over the cheeks and erythema over the served, as well (Figure 3). nasal tip. The lab studies revealed leucopenia with lymphopenia (white blood cells (WBC) 3.7x109/L; absolute lymphocyte count (ALC) 0.78x109/L), mild anemia (hemoglobin (Hb) 109 g/l), slightly elevated erythrocyte sedimentation rate (ESR 18 mm/h) with normal C-reactive protein (CRP 0.9 mg/l), slightly positive antinuclear antibodies (ANA) titer (ANA 1:160) and negative anti‐double‐stranded DNA and antiphospholipid antibodies. At this time point the parents were advised for a follow-up of the child by a pediatric rheumatologist. On discharge treatment with Figure 1: Heliotrope rash nonsteroidal anti-inflammatory drug was initiated. Methotrex- ate was prescribed as well, but the parents refused the treatment and decided to try alternative therapy (homeopathy). In the following months the child deteriorated with per- sistent arthralgia, progressive muscle weakness, difficult walking, persistent fever, progressive weight loss, and alopecia. In August 2015 the girl experienced a prolonged ultra- violet radiation exposure due to a summer holiday at the seaside. The child was out in direct sun at the beach. Despite difficulty walking, the parents were bringing the child with the help of a Figure 2: Gottron’s papules JScholar Publishers J Rheumatol Arthritis 2021 | Vol 1: 101 3 Figure 3: Skin ulcerations Clinical features were consistent with a diagnosis of Figure 5: Enhancement of subcutaneous tissue after contrast administration JDM. Of note, the creatine kinase was within normal limits (CPK 137 U/l (<142 U/l)). Levels of the other muscle enzymes were On the image after contrast administration a contrast elevated with AST (aspartate transaminase) of 925 U/l (<50 U/l), enhancement of the subcutaneous tissue, muscle fascia and the ALT (alanine transaminase) of 162 U/L (< 36 U/l), and LDH muscles was noticed (Figure 5). (lactate dehydrogenase) of 1058 U/l (260-690 U/l). The inflam- matory (ESR 34 mm/h and CRP 4.0 mg/l) and immunology (im- Moreover, the diagnosis was complicated by additional munoglobulin (Ig)A, IgM, complement components C3 and C4, clinical and laboratory findings. Jaundice of the sclera and dif- аnti-dsDNA (anti-double stranded DNA), anti-RNP (anti-ribo- fusely over the skin was noticed. On abdominal physical exam nucleoprotein), аnti-Sm (anti-Smith), аnti-SS-A (anti-Sjogren’s enlarged liver (3 cm below the costal margin) and spleen (2 cm Syndrome A), anti-SS-B (anti-Sjogren’s Syndrome B), аnti-Scl-70 below the costal margin) were observed. The hepatosplenomeg- (anti-Scleroderma-70), and аnti-Jo-1 (anti-histidyl-tRNA syn- aly was confirmed by abdominal ultrasound. The laboratory thetase) antibodies) markers were in reference ranges, apart studies revealed signs of hepatitis and cholestasis (AST 925 U/l, from slightly elevated ANA - 1:160 and elevated IgG - 23.1 g/l. ALT 162 U/l, GGT (gamma-glutamyl transferase) 282 U/l, ALP (alkaline phosphatase) 253 U/l, total bilirubin 155 µmol/l, direct This patient was also noted to have subtle arthritis with bilirubin 102/142 µmol/l). Infectious causes of hepatitis were flexion contractures at the elbows and knees, alopecia, butter- ruled out with no serological evidence of HAV (hepatitis A virus; fly-like rash and aphthous stomatitis, which are features less spe- negative IgM HAV antibodies), HBV (hepatitis B virus; negative cific to JDM but have been described previously [16,17]. HBsAg), HCV (hepatitis C virus; negative anti HCV), CMV (cy- tomegalovirus; negative