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 Table of Contents  
Year : 2022  |  Volume : 2  |  Issue : 1  |  Page : 6-9

Necrotizing Myopathy with Abundant Macrophages in Childhood Systemic Lupus Erythematosus

1 Pediatric Rheumatology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
2 Musculoskeletal Radiology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
3 Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
4 Pediatric Rheumatology, King Faisal Specialist Hospital and Research Center; College of Medicine, Alfaisal University, Riyadh, Saudi Arabia

Date of Submission27-Sep-2021
Date of Decision27-Sep-2021
Date of Acceptance06-Nov-2021
Date of Web Publication25-May-2022

Correspondence Address:
Dr. Sulaiman M Al-Mayouf
Department of Pediatrics, King Faisal Specialist Hospital and Research Center, College of Medicine, Alfaisal University, Po Box 3354, Riyadh 11211
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ara.ara_6_21

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Childhood systemic lupus erythematosus (cSLE) is a heterogeneous complex multisystem disease with substantial complications. We report a girl with refractory SLE developed myalgia and muscle weakness involving proximal and distal lower extremities as a sequel of macrophage activation syndrome. Muscle biopsy and proper staining revealed a rare necrotizing myopathy with interstitial macrophages which expands the differential diagnosis of inflammatory muscle disease in cSLE.

Keywords: Inflammatory myopathy with abundant macrophages, macrophage activation syndrome, necrotizing myopathy, systemic lupus erythematosus

How to cite this article:
Mirza A, Alyaeesh S, Albalawi A, Alismail K, Al-Hindi H, Alsonbul A, Al-Mayouf SM. Necrotizing Myopathy with Abundant Macrophages in Childhood Systemic Lupus Erythematosus. Ann Rheumatol Autoimmun 2022;2:6-9

How to cite this URL:
Mirza A, Alyaeesh S, Albalawi A, Alismail K, Al-Hindi H, Alsonbul A, Al-Mayouf SM. Necrotizing Myopathy with Abundant Macrophages in Childhood Systemic Lupus Erythematosus. Ann Rheumatol Autoimmun [serial online] 2022 [cited 2022 Dec 10];2:6-9. Available from: http://www.ara.ssr.com/text.asp?2022/2/1/6/345952

  Introduction Top

Systemic lupus erythematosus (SLE) is a complex autoimmune disease of unknown precise etiology with multiorgan involvement and unpredictable course.[1] Conventionally, childhood SLE (cSLE) has more severe disease and variable long-term outcome.[2] Despite advances in the management of cSLE, however, serious fatal complications may develop during the early phase of the disease, particularly of the refractory cases. Among the life-threatening complications reported in cSLE is macrophage activation syndrome (MAS) which is a hyperinflammatory status because of uncontrolled cytokine storm. Patients with MAS are usually presented with severe systemic clinical features associated with pancytopenia, transaminitis, and hyperferritinemia.[3],[4] Inflammatory myopathy with abundant macrophages (IMAM) is a rare distinct entity of inflammatory myopathy which is usually identified in patients with idiopathic inflammatory myopathy and rarely with other autoimmune diseases such as adult-onset Still's disease, especially in the presence of MAS.[5],[6],[7] We describe here a girl with severe cSLE who developed MAS and atypical muscle weakness. Muscle biopsy revealed necrotizing myopathy which is a rare myopathy characterized by interstitial macrophages, segmental necrosis and regeneration, and lack of mononuclear inflammatory infiltrates. Although MAS is not uncommon in cSLE, the complication of necrotizing myopathy in patients with cSLE is rare. This observation may expand the features of inflammatory muscle disease in cSLE.

  Case Report Top

A previously healthy 13-year-old girl presented to a local hospital with a 1-month history of generalized fatigue and myalgia of back and lower extremities. Her symptoms gradually progressed and subsequently evolved to include persistent high-grade fever unresponsive to antipyretics and worsening dyspnea. Family history revealed that parents and other siblings were healthy, with unremarkable familial autoimmune diseases. Initial examination on arrival at our institution was remarkable for fever (39.4°C), tachypnea (36 breaths/min), oxygen saturation (86%) while breathing room air, tachycardia (133 beats/min), and hypertension (157/72 mmHg). Glasgow Coma Scale (GCS) was 15/15. She had facial rash consistent with malar rash and oral ulceration. Chest examination revealed bilateral rhonchi, inspiratory crackles, and reduced breath sounds, with normal cardiac examination. She had hepatomegaly, but no palpable spleen or lymphadenopathy has been appreciated. The remainder of her physical examination findings was unremarkable. Initial investigations showed pancytopenia with elevated inflammatory markers and positive Coomb's test. She had renal impairment with high urea and serum creatinine levels and elevated liver enzymes with findings consistent with MAS. Furthermore, she had high antinuclear antibody and anti-double-stranded DNA (anti-ds-DNA). [Table 1] summarizes the laboratory findings. Cultures were negative, and chest radiography revealed bilateral pleural effusion.
Table 1: Summary of the pertinent laboratory results

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She was admitted to the pediatric intensive care unit (PICU) as a case of cSLE with MAS and multiorgan failure. She required supplemental oxygen, supportive care, and broad-spectrum antibiotics. Intravenous pulse methylprednisolone (IVMP) (30 mg/kg/dose) therapy for three consecutive days was initiated followed by daily prednisone (2 mg/kg/day) with hydroxychloroquine (200 mg daily), cyclosporine, and intravenous immunoglobulin (2 gm/kg/dose). Unfortunately, her condition deteriorated quickly, she showed impaired consciousness level (GCS 9/15) with hypotension. She found to have bilateral pulmonary edema with worsening bilateral pleural effusion. However, echocardiography revealed normal cardiac function. She required mechanical ventilation and vasopressors. Repeated laboratory studies revealed worsening cytopenia, prompting transfusion with packed red blood cells. She received another IVMP and underwent four sessions of plasmapheresis followed by aggressive treatment with subcutaneous Anakinra injection (100 mg daily) and intravenous cyclophosphamide (500 mg/m2/dose).

The repeated respiratory culture and Gram stain revealed aspergillus species. All viral studies came back negative except cytomegalovirus (CMV) polymerase chain reaction revealed high load. Accordingly, antimicrobial treatment, including antifungal and viral agents has been adjusted. Her clinical status gradually improved, and she was extubated and discharged from PICU, but noted to have swallowing difficulty and lower extremities weakness involving proximal and distal muscles with elevated muscle enzymes (CK 547, LD 1216, AST 262). Magnetic resonance imaging (MRI) of the proximal and distal lower l extremities showed features of acute on the top of chronic myositis in her pelvic and proximal thigh muscles and foot muscles [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d. Myositis-specific antibodies (MSA) and myositis-associated antibodies (MAA) were not available in our institution at that time. Thus, MSA and MAA were not done. Computed tomography-guided needle biopsy from the right vastus lateralis muscle was performed. Histopathological findings showed marked variation in myofiber size with many atrophic fibers. These atrophic fibers were individually scattered and in small groups [[Figure 2]a, open white arrow] with elongated and angular contours. Occasional pyknotic nuclear clumps were also noted. There were scattered fibers with segmental necrosis [[Figure 2]b, asterisks] and regeneration as well as occasionally myophagocytosis [[Figure 2]a, solid white arrow and [Figure 2]c]. The endomysium was remarkable for mild fibrosis and diffuse histiocytic (macrophagic) infiltrate best seen with the histiocytic markers [Figure 2]d. There was no inflammatory infiltrate otherwise. Most atrophic fibers expressed the fast isoform of the myosin heavy chain, indicating type 2 myofiber atrophy. The patient was diagnosed with MAS and necrotizing myopathy with cSLE. Despite the intensive treatment of MAS her condition deteriorated, she returned to PICU with a stormy course which was complicated by prolonged cardiac arrest and she passed away.
Figure 1: (a) Coronal T1WI showing diffuse subcutaneous edema and mild atrophy of the pelvic and proximal thigh muscles, hip joints are congruent. (b) Coronal STIR showing diffuse subcutaneous and muscles edema, physiologic hip joints fluid. (c) Short-axis T1WI showing subcutaneous edema and mild atrophy of the foot muscles, the bone marrow signal is normal. (d) Short axis T2WI with fat suppression showing subcutaneous edema and mild atrophy of the foot muscles, the bone marrow signal is normal

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Figure 2: (a) A necrotic myofiber is noted on the longitudinal section (solid white arrow) filled with foamy macrophages (myophagocytosis) and a group of severely atrophic myofibers with nuclear clumping are noted in the right part of the image (open white arrow), interstitial macrophages are barely seen by conventional stains (open black arrows). (b) This image shows two necrotic myofibers in cross section (asterisks) in the upper half and myofibers with internalized nuclei in the lower half. (c) A necrotic fiber with myophagocytosis is noted on the cross section. (d) Immunohistochemical stain for the histiocyte marker, CD163 highlighting the interstitial macrophages. A focus of myophagocytosis is seen in the inset

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  Discussion Top

MAS is a serious sequel of childhood rheumatic diseases. It occurs more frequently in systemic-onset juvenile idiopathic arthritis followed by cSLE.[4],[8] It is challenging to distinguish the manifestations of MAS and its consequence from the flare of SLE, particularly both conditions are associated with pancytopenia and other blood derangements. SLE is a multisystem disorder that expected to affect skeletal muscles and results in inflammatory myositis. Recent report revealed that 6.3% of SLE patients presented with concurrent inflammatory myositis. Interestingly, nonspecific inflammatory changes were the most commonly feature.[9] A spectrum of rare entities of myopathy, including IMAM and immune-mediated necrotizing myopathy, are usually identified in patients with dermatomyositis and rarely with other autoimmune and autoinflammatory diseases.[5],[6],[7],[10],[Z11] These rare myopathies are distinguished from idiopathic inflammatory myositis by predominance of myofiber necrosis and lack of mononuclear inflammatory cells.[12]

In our patient, necrotizing myositis secondary to MAS developed as a complication of the underlying disease. Considering the MRI findings, this could be happened either at the onset or during the disease course of SLE. However, the unavailability of MSA and MAA is a limitation because certain type of MSA can present with immune-mediated necrotizing myopathy and other MSA present with overlap syndromes. The coexistence of infections (aspergillus species and CMV) was due to the immunocompromised status associated with the underlying disease and the provided medications and unlikely to be the triggers of MAS and its sequel. It was previously reported that the presence of MAS was significantly associated with in-hospital mortality in febrile SLE patients, and the overall survival rate was significantly lower in SLE patients with MAS than without MAS.[13]

We previously reported a rare inflammatory myositis in a girl with SLE who proved to have autosomal recessive ISG15 deficiency underlies type I interferonopathy.[14] A major limitation of identification of SLE patients with necrotizing myositis associated with MAS is the similarity of laboratory findings between SLE and MAS. Our current case shows the rarity of this type of myositis, and the peculiar presentation of distal muscle involvement expands the features of inflammatory muscle disease in cSLE.

Ethics statement

All procedures described in this manuscript were performed in accordance with the ethical standards. Informed consent was obtained from the patient's parents for blood and tissue biopsy. Furthermore, informed consent has been obtained from the parents to access and collect the data from the medical record to be used in scientific publications.

Declaration of patient consent

The authors certify that they had obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initial will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Pan L, Lu MP, Wang JH, Xu M, Yang SR. Immunological pathogenesis and treatment of systemic lupus erythematosus. World J Pediatr 2020;16:19-30.  Back to cited text no. 1
Morgan TA, Watson L, McCann LJ, Beresford MW. Children and adolescents with SLE: Not just little adults. Lupus 2013;22:1309-19.  Back to cited text no. 2
Borgia RE, Gerstein M, Levy DM, Silverman ED, Hiraki LT. Features, treatment, and outcomes of macrophage activation syndrome in childhood-onset systemic lupus erythematosus. Arthritis Rheumatol 2018;70:616-24.  Back to cited text no. 3
Naveen R, Jain A, Muhammed H, Gupta L, Misra DP, Lawrence A, et al. Macrophage activation syndrome in systemic lupus erythematosus and systemic-onset juvenile idiopathic arthritis: A retrospective study of similarities and dissimilarities. Rheumatol Int 2021;41:625-31.  Back to cited text no. 4
Brunn A, Hans VJ, Vogelgesang S, Deckert M. Inflammatory myopathy with abundant macrophages and dermatomyositis: Two stages of one disorder or two distinct entities? Acta Neuropathol 2009;118:793-801.  Back to cited text no. 5
Rinnenthal J, Goebel H, Preuße C, Lebenheim L, Schumann M, Moos V, et al. Inflammatory myopathy with abundant macrophages (IMAM): The immunology revisited. Neuromuscul Disord 2014;24:151-5.  Back to cited text no. 6
Umeda M, Origuchi T, Fujikawa K, Koga T, Mizokami A, Nakashima Y, et al. Hemophagocytic syndrome and inflammatory myopathy with abundant macrophages in a patient with adult-onset Still's disease. Intern Med 2014;53:2385-9.  Back to cited text no. 7
Aytaç S, Batu ED, Ünal Ş, Bilginer Y, Çetin M, Tuncer M, et al. Macrophage activation syndrome in children with systemic juvenile idiopathic arthritis and systemic lupus erythematosus. Rheumatol Int 2016;36:1421-9.  Back to cited text no. 8
Bitencourt N, Solow EB, Wright T, Bermas BL. Inflammatory myositis in systemic lupus erythematosus. Lupus 2020;29:776-81.  Back to cited text no. 9
Fujikawa K, Migita K, Shigemitsu Y, Umeda M, Nonaka F, Tamai M, et al. MEFV gene polymorphisms and TNFRSF1A mutation in patients with inflammatory myopathy with abundant macrophages. Clin Exp Immunol 2014;178:224-8.  Back to cited text no. 10
Bassez G, Authier FJ, Lechapt-Zalcman E, Delfau-Larue MH, Plonquet A, Coquet M, et al. Inflammatory myopathy with abundant macrophages (IMAM): A condition sharing similarities with cytophagic histiocytic panniculitis and distinct from macrophagic myofasciitis. J Neuropathol Exp Neurol 2003;62:464-74.  Back to cited text no. 11
Ellis E, Ann Tan J, Lester S, Tucker G, Blumbergs P, Roberts-Thomson P, et al. Necrotizing myopathy: Clinicoserologic associations. Muscle Nerve 2012;45:189-94.  Back to cited text no. 12
Ahn SS, Yoo BW, Jung SM, Lee SW, Park YB, Song JJ. In-hospital mortality in febrile lupus patients based on 2016 EULAR/ACR/PRINTO classification criteria for macrophage activation syndrome. Semin Arthritis Rheum 2017;47:216-21.  Back to cited text no. 13
Al-Mayouf SM, Akbar L, AlEnazi A, Al-Mousa H. Autosomal recessive ISG15 deficiency underlies type I interferonopathy with systemic lupus erythematosus and inflammatory myositis. J Clin Immunol 2021;41:1361-4.  Back to cited text no. 14


  [Figure 1], [Figure 2]

  [Table 1]


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