This article originally appeared on the Hospital for Special Surgery website.
In May 2019, a 32-year-old woman developed a rash on her face, chest, and knuckles, initially thought to be contact dermatitis. She saw a second dermatologist to evaluate persistent symptoms, who found positive results on antinuclear antibody (ANA) testing. She was referred to rheumatology, but additional lab testing was unrevealing. She learned that she was pregnant, and the rash resolved spontaneously 4 weeks into the pregnancy. She delivered a heathy son at 40 weeks' gestation. Approximately 8 weeks postpartum, the rash on her face, chest, and knuckles recurred. About 4.5 months postpartum, she developed fatigue and weakness of her proximal arms and legs, and came to HSS for evaluation. She had no shortness of breath or dysphagia.
The patient had a prior uncomplicated pregnancy, no prior surgeries, and no family history of autoimmunity, but she did have a first-degree relative with a BRCA mutation. She was breastfeeding and planned to wean in the setting of possibly needing additional medications. She was married, with two young children, and worked full-time.
Her physical exam was notable for erythema of her cheeks and upper chest, with erythematous papules over the metacarpophalangeal joints, consistent with Gottron papules. She could not abduct her shoulders above 90° against gravity, although she could stand from a seated position without using her arms.
Laboratory testing showed a white blood cell count of 3.3 cells/mm3 and elevated levels of aspartate aminotransferase (45 U/L), creatine kinase (CK, 665 U/L), aldolase (10.6 U/L), and lactate dehydrogenase (LDH, 324 U/L). An ANA test was positive in a speckled pattern at a 1:320 dilution, while tests of anti-Jo-1, anti-RNP, and anti-dsDNA antibodies were negative, complement C3 and C4 were normal, and erythrocyte sedimentation rate was normal. Myositis autoantibody profiling was positive for p155/140 (TIF-1gamma). A skin biopsy result was consistent with dermatomyositis (Figures 1 and 2). Pulmonary function testing and echocardiography were normal.
Figure 1. Hematoxylin and eosin staining of biopsy demonstrates dermatomyositis.
Figure 2. MxA staining, which binds to endothelial cells.
She was started on high-dose prednisone, with rapid, significant partial improvement in strength and skin disease. Azathioprine 50 mg daily was then added. Over the next several weeks, her strength continued to improve and the rash continued to fade, and CK and LDH levels fell. Intravenous immunoglobulin (IVIG) 2 g/kg monthly was added for additional steroid sparing and symptom control, and she noted further skin improvement. A second series of IVIG doses unfortunately was associated with development of aseptic meningitis requiring hospitalization.
Malignancy screening was performed. CT scanning of the chest/abdomen/pelvis was normal. Esophagogastroduodenoscopy and colonoscopy revealed features of celiac disease and lymphocytic colitis. Mammography showed changes consistent with lactation. Genetic testing disclosed no BRCA1/2 mutations but did show a mutated checkpoint kinase 2 (CHEK2) allele, which is associated with an increased risk for ovarian, colon, and breast cancers.
Pregnancy outcomes in myositis are variable, but good outcomes are associated with proper disease control prior to pregnancy, as in other rheumatic diseases such as lupus. It has long been recognized that a subset of patients with rheumatoid arthritis do particularly well during pregnancy, achieving reduced disease activity, or even remission, though they may flare again postpartum. Our case demonstrates this spontaneous improvement phenomenon manifesting in dermatomyositis, which has been described in a small Spanish case series but is nonetheless very rare.
Anti-TIF-1gamma antibodies are specific to patients with dermatomyositis, most commonly patients with malignancy-associated dermatomyositis. In a recent large study, 38% of patients positive for anti-TIF-1gamma developed cancer, vs 15% of patients who were anti-TIF-1gamma negative. While our patient did not exhibit signs of malignancy after comprehensive screening, the risk for an occult malignancy emerging remains elevated in patients with anti-TIF-1gamma for 3 years after dermatomyositis disease onset.
Ongoing screening is merited over that period in these patients. However, the risk for malignancy in this context is also tightly related to age. Juvenile dermatomyositis poses essentially no risk for malignancy, and malignancy risk remains low but not nonexistent in those under 40 years of age. Our patient will continue with intensive lifelong screening for malignancy based on the presence of a heterozygous mutation in the tumor-suppressor gene CHEK2, which has been implicated in increased risk for several cancers, including breast cancer.
This case illustrates several interesting features of rheumatic disease during pregnancy, as well as the use of autoantibody testing to identify patients at high risk for malignancy-associated dermatomyositis, who would benefit from more prolonged surveillance.
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Cite this: The Use of Autoantibody Testing in a Postpartum Patient at Risk for Malignancy-Associated Dermatomyositis - Medscape - May 04, 2021.