Sex: F
Vaccine: COVID19
Symptoms: Complement factor C4, Computerised tomogram abdomen, Computerised tomogram pelvis, Computerised tomogram thorax, Coxsackie virus test
Clinical narrative: amyopathic DM with rapidly progressive interstitial lung disease; amyopathic DM with rapidly progressive interstitial lung disease; This is a literature report.  A female patient in her 60's received BNT162b2 (BNT162B2), as dose 2, single (Batch/Lot number: unknown) for covid-19 immunisation. The patient's relevant medical history and concomitant medications were not reported. The following information was reported: DERMATOMYOSITIS (medically significant, life threatening), INTERSTITIAL LUNG DISEASE (medically significant, life threatening), all with latency 2 weeks after the suspect product(s) administration, outcome "recovering" and all described as "amyopathic DM with rapidly progressive interstitial lung disease". The patient underwent the following laboratory tests and procedures: Alanine aminotransferase (0-32): 123 IU/l, notes: Initial labs 0-37; 67 IU/l, notes: 3 months; 26 IU/l, notes: 6 months; Albumin globulin ratio (1.2-2.2): 1.2, notes: Initial labs; 1.1, notes: 3 months; 0.7, notes: 6 months; Aldolase (3.3-10.3): 8.5 IU/l, notes: Initial labs 1.5-8.1; 9.0 IU/l, notes: 6 months; Antibody test: Negative, notes: Initial labs; Negative, notes: Initial labs; Negative, notes: Initial labs; Antibody test (normal high range 20): 113, notes: Initial labs unit: AU/mL; 27, notes: 3 months; less than 20 Neg, notes: 6 months; Negative, notes: Initial labs; 26, notes: Initial labs Neg less than 20, strong pos greater than 59; Antibody test (0.00-0.90): less than 0.91, notes: Initial labs (ISR); Negative, notes: Initial labs; Negative, notes: Initial labs; Negative, notes: Initial labs; Antineutrophil cytoplasmic antibody (0.0-0.9): less than 9.0, notes: Initial labs; Antineutrophil cytoplasmic antibody (0.0-3.5): less than 3.5, notes: Initial labs; Antineutrophil cytoplasmic antibody: Neg less than 1.2 titer, notes: Initial labs; less than 1.20, notes: 3 months; Neg less than 1.2 titer, notes: Initial labs; less than 1.20, notes: 3 months; Antinuclear antibody: Negative, notes: Initial labs; Negative, notes: Initial labs; Antinuclear antibody (0-40): 120, notes: Initial labs less than 20,less than 29 Neg; 49, notes: 3 months; 29, notes: 6 months; less than 20, notes: Initial labs less than 20; 23, notes: 3 months; Negative, notes: 6 months; Negative, notes: Initial labs less than 20; Negative, notes: 3 months; Negative, notes: 6 months; Negative, notes: Initial labs less than 20; Negative, notes: 3 months; Negative, notes: 6 months; Anti-thyroid antibody (0.0-0.9): less than 1, notes: Initial labs; Anti-thyroid antibody (0-34): 12 IU/ml, notes: Initial labs; Aspartate aminotransferase (0-40): 164 IU/l, notes: Initial labs 5-34; 59 IU/l, notes: 3 months; 36 IU/l, notes: 6 months; Basophil count (0-1): 0, notes: Initial labs Not estab; 0, notes: 3 months; 0, notes: 6 months; Biopsy skin: revealed interface dermatitis; Blood albumin (3.8-4.8): 3.6 g/dl, notes: Initial labs 3.5-5.2; 3.1 g/dl, notes: 3 months; 3.4 g/dl, notes: 6 months; Blood alkaline phosphatase (48-121): 79 IU/l, notes: Initial labs 40-150; 69 IU/l, notes: 3 months; 44 IU/l, notes: 6 months; Blood bilirubin (0.0-1.2): 0.4 mg/dl, notes: Initial labs 0.2-1.2; 0.4 mg/dl, notes: 3 months; 0.6 mg/dl, notes: 6 months; Blood calcium (8.7-10.3): 8.8 mg/dl, notes: Initial labs 8.4-10.4; 8.4 mg/dl, notes: 3 months; 9.1 mg/dl, notes: 6 months; Blood chloride (96-106): 100 mmol/L, notes: Initial labs 98-107; 91 mmol/L, notes: 3 months; 103 mmol/L, notes: 6 months; Blood creatine phosphokinase: normal; Blood creatine phosphokinase (32-182): 163 IU/l, notes: Initial labs 29-168; 44 IU/l, notes: 6 months; Blood creatinine (0.57-1.00): 0.62 mg/dl, notes: Initial labs 0.6-1.1; 0.58 mg/dl, notes: 3 months; 0.73 mg/dl, notes: 6 months; Blood glucose (65-99): 94 mg/dl, notes: Initial labs 70-100; 91 mg/dl, notes: 6 months; Blood potassium (3.5-5.2): 4.6 mmol/L, notes: Initial labs 3.5-4.8; 4.2 mmol/L, notes: 6 months; Blood sodium (134-144): 134 mmol/L, notes: Initial labs 136-145; 127 mmol/L, notes: 3 months; 137 mmol/L, notes: 6 months; Blood thyroid stimulating hormone (0.450-4.500): 1.8 IU/ml; Blood urea (8-27): 12 mg/dl, notes: Initial labs; 21 mg/dl, notes: 3 months; 19 mg/dl, notes: 6 months; Carbon dioxide (20-29): 23 mmol/L, notes: Initial labs; 20 mmol/L, notes: 3 months; 22 mmol/L, notes: 6 months; Complement factor C3 (82-167): 97 mg/dl, notes: Initial labs; Complement factor C4 (12-38): 42 mg/dl, notes: Initial labs; Computerised tomogram abdomen: normal; Computerised tomogram pelvis: normal; Computerised tomogram thorax: Multifocal scattered GGOs and, notes: sub solid opacities in peripheral; Moderately increased GGOs and, notes: sub-solid opacities; Less GGOs, more dense fbrotic, notes: changes; Signifcant improvement GGOs; abnormal; Coxsackie virus test (normal high range 1:100): 1:1600, notes: Initial labs; Coxsackie virus test (normal high range 1:10): Negative, notes: Initial labs; C-reactive protein (0-10): less than 1, notes: Initial labs 0-5; less than 1, notes: 6 months; Cryptococcus test: Negative, notes: Initial labs; Double stranded DNA antibody: Negative; Eosinophil count (1-6): 1 %, notes: Initial labs Not estab; 0 %, notes: 3 months; 0 %, notes: 6 months; Forced expiratory volume: 70 %; 64 %; 60 %; 66 %; 70 %; 83 %; 88 %; Forced vital capacity: 71 %; 64 %; 55 %; 60 %; 65 %; 78 %; 83 %; Full blood count: normal; Globulin (1.5-4.5): 2.9 g/dl, notes: Initial labs; 2.7 g/dl, notes: 3 months; 4.6 g/dl, notes: 6 months; Glomerular filtration rate (normal low range 59): 96, notes: Initial labs unit:mL/min/1.73 greater than 60; 98, notes: 3 months; 87, notes: 6 months; Haematocrit (34.0-46.6): 32.5 %, notes: 34-45 Initial labs; 38 %, notes: 3 months; 35.9 %, notes: 6 months; Haemoglobin (11.1-15.9): 11.1 g/dl, notes: 11.2-15.7 Initial labs; 12.8 g/dl, notes: 3 months; 12.3 g/dl, notes: 6 months; Hepatitis A antibody: Negative, notes: Initial labs; Hepatitis B core antibody: Negative, notes: Initial labs; Hepatitis B surface antigen: Negative, notes: Initial labs; Hepatitis C antibody (0.0-0.9): less than 0.1, notes: unit: (s/co ratio); 6MWT: 89; No O2; No O2; Blastomyces Abs, Qn, DID (normal high range 1:1): Negative, notes: Initial labs; Histoplasma Galmannan Ag Ur (normal high range 0.5): Negative, notes: Initial labs; Negative, notes: Initial labs; Negative, notes: Initial labs; Sedimentation rate-Westergren (0-40): 76, notes: Initial labs unit: mm/h; 66, notes: 6 months; 76, notes: unit: mm/h; elevated; Negative, notes: Initial labs; Liver function test: elevated; Lung diffusion test: 31 %; 57 %; 64 %; 67 %; 81 %; Lymphocyte count (19-52): 22 %, notes: Initial labs Not estab; 5 %, notes: 3 months; 11 %, notes: 6 months; Mean cell volume (79-97): 90, notes: Initial labs Unit: fL 79-95; 97, notes: 3 months; 95, notes: 6 months; Monocyte count (5-13): 15 %, notes: Initial labs Not estab; 7 %, notes: 3 months; 3 %, notes: 6 months; Neutrophil count (34-71): 60 %, notes: Initial labs Not estab; 86 %, notes: 3 months; 86 %, notes: 6 months; physical exam: was notable for normal, notes: cardiovascula and neurologic exam, lungs with mild bibasilar  crackles, and skin rash suspicious for dermatomyositis; Platelet count (150-450): 298, notes: Initial labs Unit: x 10E3/µL 150-400; 225, notes: 3 months; 251, notes: 6 months; Protein total (6.0-8.5): 6.5 g/dl, notes: 6.7-8.6 Initial labs; 5.8 g/dl, notes: 3 months; 8.0 g/dl, notes: 6 months; Rheumatoid factor (0.0-13.9): less than 10.0; SARS-CoV-2 antibody test: Negative, notes: Initial labs; Negative, notes: Initial labs; SARS-CoV-2 test: Negative, notes: Initial labs; Serum ferritin (15-150): 1183 ng/ml, notes: 3 months; Total lung capacity: 102; 83; 81; 70; 87; 87; 102; Treponema test: Non-reactive, notes: Initial labs; Ultrasound abdomen: normal; Vitamin D (30.0-100.0): 32.6 ng/ml, notes: Initial labs; White blood cell count (3.4-10.8): 5.3, notes: unit:*10E3/µL, 4-10 Initial labs; 10.3, notes: 3 months; 7.3, notes: 6 months; Ultrasound pelvis: normal. Therapeutic measures were taken as a result of dermatomyositis, interstitial lung disease. The patient is a previously healthy woman in her early 60s who developed diffuse rash two weeks after receiving the second dose of COVID-19 mRNA vaccine. The rash was non-pruritic, painless, and covered her upper extremities, torso, palmar and dorsum of hands, chest wall, neck, bilateral eyelids, and edge of her mouth. She was initially diagnosed with Coxsackie A infection based on positive Coxsackie A IgG antibody. Her rash continued to worsen and within two weeks, she started to have significant dyspnea on exertion with frequent coughing spells. She also reported profound fatigue but denied fevers, chills, sputum production, and history of Raynaud's or sicca symptoms. She denied recent travels, sick contacts, or prior history of COVID infection. She has no relevant family history. Her physical exam was notable for normal cardiovascular and neurologic exam, lungs with mild bibasilar crackles, and skin rash suspicious for dermatomyositis including Gottron's papules (erythematous papules overlying metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints), Shawl sign on her chest wall and neck, and heliotrope rash with associated eyelid and facial swelling. She also had small ulcers on her lower lip and erythematous papules on the palmar surface of her hands. Interestingly, she had symmetric joint swelling in her wrists, elbows, and MCP and PIP joints without complaint of joint pain. She had a normal nailfold capillaroscopy exam. Her strength testing in all muscle groups was within normal limits. Initial laboratory testing was notable for normal blood counts, elevated liver function tests, normal creatine kinase and aldolase, and elevated segmentation rate (76 mm/h). Antinuclear antibody (ANA), ANA comprehensive panel, and rheumatoid factor were negative, and cyclic citrullinated peptide (CCP) antibody was mildly elevated. Fungal infections ruled out with negative urine Histoplasma antigen enzyme immunoassay, Blastomyces antibodies, and serum Cryptococcus antigen. Her COVID-19 rapid antigen tests and COVID-19 IgM antibody were negative. Rocky Mountain spotted fever and syphilis screening tests were non-reactive. Skin biopsy revealed interface dermatitis. Pulmonary function tests (PFTs) showed forced vital capacity (FVC) 71% (normal range: 80 to 120%), forced expiratory volume during first second (FEV1) 70%, and diffuse capacity for carbon monoxide (DLCO) 31% and computed tomography (CT) of the chest had ground-glass opacities (GGOs) in the subpleural distribution. Malignancy was ruled out with normal abdominal ultrasound, pelvis ultrasound, and CT of the abdomen and pelvis. MRI of the thighs and electromyography (EMG) were deferred given normal strength testing and muscle enzyme levels. One week after presentation, her Myomarker panel came back with positive anti-MDA-5 antibody 113 (normal value less than 20 units) and anti-SSA 52KD antibody IgG 120 (normal value less than 20 units). In differential diagnosis, the patient's primary care physician initially diagnosed her with Coxsackie A infection given her palmar rash and positive Coxsackie A IgG antibody. She was expected to improve with time, but her rash worsened, and she developed abnormal lung findings. Sarcoidosis was considered but her skin rash was atypical for sarcoidosis, and she did not have mediastinal or hilar lymphadenopathy. Differential diagnosis also included serum sickness-like syndrome following vaccination given skin rashes and symmetric polyarthritis. However, the patient did not have fevers and her rash was more consistent with dermatomyositis than typical urticarial rash in serum sickness-like reactions. Given the diffuse GGO on CT of the chest, interstitial lung disease (ILD) with nonspecific interstitial pneumonia (NSIP) or organizing pneumonia pattern was high on the differential but infections had to be ruled out before initiation of immunosuppression. Disseminated fungal infections can also present with acute and chronic lung diseases. Acute pneumonia from blastomycosis often presents with fever and nonproductive cough and CT of the chest may show nodules, consolidations with or without cavitation, and/or tree in bud opacities. Pulmonary histoplasmosis can mimic sarcoidosis with diffuse pulmonary infiltrates and mediastinal or hilar lymphadenopathy, and cavitary lung disease in chronic cases. Pulmonary cryptococcosis can be asymptomatic in immunocompetent adults and radiographic findings include noncalcified nodules, lobar infiltrates, hilar and mediastinal adenopathy, and pleural effusions. The author's patient did not live in an endemic area for fungal infections, and active fungal infections were ruled out with blood and urine testing. Given the diffuse GGOs and abnormal PFTs, COVID-19 pneumonia was also on the differential. She had multiple negative rapid antigens testing for COVID-19 and negative COVID-19 IgM antibody and nucleocapsid IgG antibody. The author diagnosed the patient with MDA-5-positive amyopathic DM with rapidly progressive interstitial lung disease (RP-ILD) based on her characteristic DM rashes with skin biopsy showing interface dermatitis, abnormal CT of the chest/PFT findings, and high titer MDA-5 antibodies. In treatment course, after fungal infections were ruled out, she was promptly started on methylprednisolone 1 mg/kg with slight improvement in her dyspnea on exertion and energy level. Given her extensive lung disease, she was started on combination therapy that consisted of rituximab infusions 1000 mg every 2 weeks spaced 6 months apart and mycophenolate mofetil (MMF) titrated to 1500 mg BID. Combination therapy rituximab plus MMF was chosen over cyclophosphamide due to a more favorable side effect profile and a reported good outcome achieved in a similar case of antisynthetase syndrome with RP-ILD. For her extensive skin involvement, she also received intravenous immunoglobulin (IVIG) 2 g/kg divided over 3 days every 4 weeks. Methylprednisolone was tapered slowly based on treatment response by approximately 8 mg every month. The patient was concomitantly treated with trimethoprim/ sulfamethoxazole for Pneumocystis jirovecii pneumonia (PJP) prophylaxis, calcium/vitamin D, and received one dose of IV zolendronic acid 5 mg. Despite initial aggressive treatment, the patient had worsening of GGO on CT of the chest and slightly worse PFTs with oxygen requirement on the six-minute walk test during the first 2 months. However, on her third month follow-up, she demonstrated mild clinical improvement with slightly less GGO on CT of the chest and stabilization of PFTs. Approximately 6 months after diagnosis, she had normalization of PFTs and significant improvement of pulmonary infiltrates on CT of the chest. Her dermatomyositis rash improved drastically as well with near complete resolution. Interestingly, her MDA-5 antibody titers decreased to 27 (less than 20 units) at 3 months and to undetectable level by 6 months. In discussion, the author described a rare case of new-onset MDA-5-positive dermatomyositis with rapidly progressive interstitial lung disease two weeks after receiving the second dose of COVID-19 mRNA vaccination. The patient had classic dermatomyositis rashes (Gottron's papules, shawl sign, and heliotrope rash), no evidence of muscle involvement, and RP-ILD associated with high titer MDA-5 antibodies. Her ILD and rash improved with aggressive combination therapy including high-dose steroids, rituximab, mycophenolate mofetil, and IVIG. Interstitial lung disease (ILD) is a major cause of morbidity and mortality among patients with dermatomyositis or polymyositis. Anti-MDA-5 syndrome is a rare presentation of idiopathic inflammatory myositis associated with rapidly progressive course of ILD and poor prognosis. The target antigen is the ribonucleic acid (RNA) helicase encoded by the melanoma differentiation-associated gene 5, which is an intracellular sensor of viral RNA (including coronavirus) that triggers the innate immune and subsequent production of cytokines including type I interferon, tumor necrosis factor alpha (TNFa), interleukin-1 (IL-1), IL-6, and IL-18. The proposed pathogenesis involves a role of infectious and environmental factors superimposed on a genetic susceptibility. RNA viruses such as Coxsackie virus and parvovirus B19 have been implicated in causation of DM in the past. Clinically, anti-MDA-5 DM has unique features of cutaneous vasculopathy and RP-ILD. In addition to classic rashes of DM, patients often have oral ulcers, palmar papules, and eyelid edema which were seen in our patient. Arthritis typically presents in symmetric distribution similar to rheumatoid arthritis in 50-80% patients with anti- MDA-5 DM. Early and aggressive treatment with a combination of immunosuppressant is critical for survival. Retrospective series suggest benefit from initial combination therapy including the use of steroids, tacrolimus, cyclophosphamide, mycophenolate mofetil, and rituximab. A recent retrospective study demonstrated adjunct IVIG therapy as a very effective first-line therapy for patients with MDA-5-RP-ILD, increasing survival and remission by lowering ferritin concentration, anti-MDA-5 titer, and GGO score on CT. Interestingly, anti-MDA-5 concentrations correlated with RP-ILD activity as well as relapse. The author's patient's anti-MDA-5 levels became undetectable after 6 months of treatment which correlated with improvement in her PFTs and radiographic imaging and resolution of her rash. Overall, the occurrence of interstitial lung disease associated with amyopathic dermatomyositis following COVID-19 vaccination is exceedingly rare and the benefits of COVID-19 vaccination far outweigh the risks. Strength of this case report included comprehensive patient information and good patient adherence to treatment and follow-up. The major limitation is the case report design which cannot prove direct causation and we can only postulate COVID-19 vaccination as a probable inciting trigger for ILD. The author's patient also tested positive for Coxsackie A which has been associated for DM as well. However, it is important to describe this interesting case to alert clinicians the possibility of ILD associated with amyopathic dermatomyositis following COVID-19 vaccination because early aggressive therapy is critical for survival and good outcomes. In conclusion, the author's described a unique case of MDA-5 syndrome with RP-ILD shortly after COVID-19 vaccination. The patient responded well to early identification and prompt aggressive immunosuppressive therapy. Larger epidemiology studies are needed to prove a causal relationship and establish surveillance for vaccine-induced immunological adverse events.; Sender's Comments: Based on the information in the case report and a plausible temporal relationship, a possible causal relationship between the events Dermatomyositis, interstitial lung disease and suspect drug BNT162B2 cannot be excluded.  The impact of this report on the benefit/risk profile of the Pfizer product is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to regulatory authorities, Ethics Committees, and Investigators, as appropriate