TY - JOUR
AU - Harigai, Masayoshi
AB - Abstract Tumour necrosis factor (TNF) inhibitors are known to induce autoimmune diseases, such as lupus-like syndrome; in rare cases, TNF inhibitor-induced myositis has been reported. This report documents the case of a male patient with ulcerative colitis (UC) complicated by TNF inhibitor-induced myositis. After UC diagnosis and treatment with azathioprine and infliximab, he was evaluated for a recent 5-month history of muscle weakness and pain. Laboratory tests revealed elevated muscle enzymes, such as serum creatine kinase (CK) and aldolase. He also tested positive for anti-nuclear antibodies and anti-double stranded DNA antibodies. High-intensity signals in his quadriceps on magnetic resonance image (MRI) and fibrillation potentials in his proximal muscles on electromyography were demonstrated. Muscle biopsy revealed the endomysial infiltration of mononuclear cells surrounding myofibers. Eventually, the patient fulfilled the classification criteria for idiopathic inflammatory myopathies. Although an adverse drug reaction of infliximab had been speculated, his muscle involvements did not improve in 6 weeks from the last administration of infliximab; therefore, treatment with prednisolone was initiated. Subsequently, his muscle symptoms ameliorated, and his serum CK levels returned to normal. Repeat MRI revealed a complete resolution of the signal intensity, and he reported no symptoms of UC or myositis while prednisolone was tapered without resumption of infliximab. Clinicians should consider the diagnosis of drug-induced myositis if muscle symptoms develop in patients treated with TNF inhibitors. Anti-double stranded DNA antibody, infliximab, myositis, tumour necrosis factor inhibitor, ulcerative colitis Introduction Tumour necrosis factor (TNF) inhibitors, such as infliximab, are widely used for treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis, and inflammatory bowel disease [1,2]. However, TNF inhibitors are known to induce autoimmune diseases, such as lupus-like syndrome, vasculitis, and interstitial lung diseases [3]. In addition, rare cases of myositis induced by TNF inhibitors have been reported [3–19]. This case report presents a patient with ulcerative colitis (UC) complicated by biopsy-proven myositis induced by infliximab. The patient was successfully treated with high-dose prednisolone after discontinuation of infliximab. Case presentation A 60-year-old Japanese man was evaluated for a 5-month history of difficulty raising his arms and muscle pain in his thighs while walking. His history was significant for UC diagnosed 8 years previously, which was treated with azathioprine 50 mg/day from the disease onset, concomitant with infliximab 5 mg/kg/infusion for the past 2 years. In addition, rosuvastatin had been administered to lower serum cholesterol. For his current presentation of musculoskeletal pain, laboratory evaluation revealed an elevation in serum creatine kinase (CK) concentration to 3860 U/L. Because statin-induced rhabdomyolysis was suspected, rosuvastatin was withdrawn. However, his serum CK levels remained high, and he was referred and admitted to the authors’ department. The last infliximab infusion he received was four weeks before the hospital admission. On admission, a 5-point manual muscle test demonstrated some weakness in the restricted muscles as follows: grade 4 only in his subscapularis muscles, small circular muscles, and subspinous muscles. Manifestations suggesting dermatomyositis, such as heliotrope rash, Gottron’s papules, and Gottron’s sign, were not observed. Köbner phenomenon or abnormal dermoscopy findings of nail fold capillaries were not observed. Laboratory tests on admission revealed an elevation in the serum levels of muscle enzymes as follows: CK (3318 U/L; normal range [NR], 62–287 U/L), aldolase (50.9 U/L [NR, 2.1–6.1 U/L]), aspartate transaminase (102 U/L [NR, 13–33 U/L]), alanine transaminase (105 U/L [NR, 6–30 U/L]), and lactate dehydrogenase (526 U/L [NR, 119–229 U/L]). In addition, as summarised in Table 1, anti-nuclear antibodies were positive at 1:320 (homogenous and speckled staining patterns), and titres of anti-double stranded DNA (anti-dsDNA) antibodies by Farr assay and anti-dsDNA IgM antibodies by enzyme-linked immunosorbent assay (ELISA) were elevated (49 IU/mL [NR ≤ 6 IU/mL], and 42 U/mL [NR < 6 U/mL], respectively). His serum also tested positive for lupus anticoagulant (1.78 [NR < 1.3]). Anti-dsDNA IgG antibodies were negative by ELISA (2.5 IU/mL [NR ≤ 12 IU/mL]). A panel of other myositis-specific and myositis-associated autoantibodies, including autoantibodies against 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR), Jo-1, “aminoacyl-tRNA synthetases (mixture of Jo-1, PL-7, PL-12, EJ, and KS)”, transcriptional intermediary factor-1-γ, melanoma differentiation associated gene 5, Mi-2, signal recognition particle, U1 small nuclear ribonucleoprotein, Ro/SS-A, showed negative results. Myeloperoxidase and proteinase3-anti-neutrophil cytoplasmic antibodies were also negative. The serum levels of thyroid and thyroid stimulating hormones were normal: free T3 (3.12 pg/mL [NR, 2.40–4.00 pg/mL], 62–287 U/L), free T4 (1.23 ng/dL [NR, 0.94–1.60 U/L]), and thyroid stimulating hormone (2.490 μIU/mL [NR, 0.380–4.300 μIU/mL]). Table 1. Summary of laboratory data. Anti-nuclear antibody 1:320 (homogenous and speckled staining patterns) Anti-dsDNA antibody by Farr assay (IU/mL) 49 Anti-dsDNA IgG antibody by ELISA (U/mL) 2.5 Anti-dsDNA IgM antibody by ELISA (U/mL) 42 Anti-Sm antibody (U/mL) <1.0 anti-U1 small nuclear ribonucleoprotein antibody (U/mL) <2.0 Anti-Jo-1 antibody (U/mL) <1.0 “Anti-ARS antibodies”* (U/mL) <1.0 Anti-transcriptional intermediary factor-1-γ antibody (index) <5 Anti-Mi-2 antibody (index) <5 Anti-melanoma differentiation associated gene 5 antibody (index) <4 Anti-HMGCR antibody (IU/mL) <1.0 Anti-signal recognition particle antibody by line blot assay negative Anti-Ro/SS-A antibody (U/mL) <1.0 β2glycoprotein 1 dependent anti-cardiolipin antibody (U/mL) 0.7 Lupus anticoagulant by dilute Russell’s viper venom time (ratio) 1.78 Myeloperoxidase-ANCA (U/mL) <1.0 Proteinase3-ANCA (U/mL) <1.0 Rheumatoid factor (U/mL) <5 Anti-cyclic citrullinated peptide antibody (U/mL) 0.6 Free T3 (pg/mL) 3.12 Free T4 (ng/dL) 1.23 Thyroid stimulating hormone (μIU/mL) 2.49 Anti-nuclear antibody 1:320 (homogenous and speckled staining patterns) Anti-dsDNA antibody by Farr assay (IU/mL) 49 Anti-dsDNA IgG antibody by ELISA (U/mL) 2.5 Anti-dsDNA IgM antibody by ELISA (U/mL) 42 Anti-Sm antibody (U/mL) <1.0 anti-U1 small nuclear ribonucleoprotein antibody (U/mL) <2.0 Anti-Jo-1 antibody (U/mL) <1.0 “Anti-ARS antibodies”* (U/mL) <1.0 Anti-transcriptional intermediary factor-1-γ antibody (index) <5 Anti-Mi-2 antibody (index) <5 Anti-melanoma differentiation associated gene 5 antibody (index) <4 Anti-HMGCR antibody (IU/mL) <1.0 Anti-signal recognition particle antibody by line blot assay negative Anti-Ro/SS-A antibody (U/mL) <1.0 β2glycoprotein 1 dependent anti-cardiolipin antibody (U/mL) 0.7 Lupus anticoagulant by dilute Russell’s viper venom time (ratio) 1.78 Myeloperoxidase-ANCA (U/mL) <1.0 Proteinase3-ANCA (U/mL) <1.0 Rheumatoid factor (U/mL) <5 Anti-cyclic citrullinated peptide antibody (U/mL) 0.6 Free T3 (pg/mL) 3.12 Free T4 (ng/dL) 1.23 Thyroid stimulating hormone (μIU/mL) 2.49 *Antigen was the mixture of several aminoacyl-tRNA synthetases, namely, Jo-1, PL-7, PL-12, EJ, and KS. dsDNA: double stranded DNA; ELISA: enzyme-linked immunosorbent assay; HMGCR: 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase; ANCA: anti-neutrophil cytoplasmic antibody. Open in new tab Table 1. Summary of laboratory data. Anti-nuclear antibody 1:320 (homogenous and speckled staining patterns) Anti-dsDNA antibody by Farr assay (IU/mL) 49 Anti-dsDNA IgG antibody by ELISA (U/mL) 2.5 Anti-dsDNA IgM antibody by ELISA (U/mL) 42 Anti-Sm antibody (U/mL) <1.0 anti-U1 small nuclear ribonucleoprotein antibody (U/mL) <2.0 Anti-Jo-1 antibody (U/mL) <1.0 “Anti-ARS antibodies”* (U/mL) <1.0 Anti-transcriptional intermediary factor-1-γ antibody (index) <5 Anti-Mi-2 antibody (index) <5 Anti-melanoma differentiation associated gene 5 antibody (index) <4 Anti-HMGCR antibody (IU/mL) <1.0 Anti-signal recognition particle antibody by line blot assay negative Anti-Ro/SS-A antibody (U/mL) <1.0 β2glycoprotein 1 dependent anti-cardiolipin antibody (U/mL) 0.7 Lupus anticoagulant by dilute Russell’s viper venom time (ratio) 1.78 Myeloperoxidase-ANCA (U/mL) <1.0 Proteinase3-ANCA (U/mL) <1.0 Rheumatoid factor (U/mL) <5 Anti-cyclic citrullinated peptide antibody (U/mL) 0.6 Free T3 (pg/mL) 3.12 Free T4 (ng/dL) 1.23 Thyroid stimulating hormone (μIU/mL) 2.49 Anti-nuclear antibody 1:320 (homogenous and speckled staining patterns) Anti-dsDNA antibody by Farr assay (IU/mL) 49 Anti-dsDNA IgG antibody by ELISA (U/mL) 2.5 Anti-dsDNA IgM antibody by ELISA (U/mL) 42 Anti-Sm antibody (U/mL) <1.0 anti-U1 small nuclear ribonucleoprotein antibody (U/mL) <2.0 Anti-Jo-1 antibody (U/mL) <1.0 “Anti-ARS antibodies”* (U/mL) <1.0 Anti-transcriptional intermediary factor-1-γ antibody (index) <5 Anti-Mi-2 antibody (index) <5 Anti-melanoma differentiation associated gene 5 antibody (index) <4 Anti-HMGCR antibody (IU/mL) <1.0 Anti-signal recognition particle antibody by line blot assay negative Anti-Ro/SS-A antibody (U/mL) <1.0 β2glycoprotein 1 dependent anti-cardiolipin antibody (U/mL) 0.7 Lupus anticoagulant by dilute Russell’s viper venom time (ratio) 1.78 Myeloperoxidase-ANCA (U/mL) <1.0 Proteinase3-ANCA (U/mL) <1.0 Rheumatoid factor (U/mL) <5 Anti-cyclic citrullinated peptide antibody (U/mL) 0.6 Free T3 (pg/mL) 3.12 Free T4 (ng/dL) 1.23 Thyroid stimulating hormone (μIU/mL) 2.49 *Antigen was the mixture of several aminoacyl-tRNA synthetases, namely, Jo-1, PL-7, PL-12, EJ, and KS. dsDNA: double stranded DNA; ELISA: enzyme-linked immunosorbent assay; HMGCR: 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase; ANCA: anti-neutrophil cytoplasmic antibody. Open in new tab A short tau inversion recovery magnetic resonance image (MRI) examination demonstrated high-intensity signals in his quadriceps muscles (Figure 1(a)). Electromyography (EMG) demonstrated fibrillation potentials in his deltoid, flexor digitorum profundus, iliopsoas, semimembranosus, vastus lateralis, tibialis anterior, and gracilis muscles. Muscle biopsy from his right vastus lateralis muscle showed the endomysial infiltration of mononuclear cells surrounding—but not invading—myofibers (Figure 2(a,b)). The perifascicular atrophy and rimmed vacuoles, which are the most characteristic histological findings for dermatomyositis and inclusion body myositis, respectively, were not observed although some perivascular infiltration of mononuclear cells were seen. The infiltrating mononuclear cells were predominantly CD4 or CD8 positive T cells (no obvious predominance in CD4/CD8). Although his muscle weakness was subtle, he fulfilled the classification criteria for idiopathic inflammatory myopathies (IIMs) [20]: age of onset of first symptom (≥40); objective symmetric weakness, usually progressive, of the proximal upper extremities; elevated serum levels of CK; endomysial infiltration of mononuclear cells surrounding, but not invading, myofibers; perivascular infiltration of mononuclear cells (score: 7.2, probability: 67%, classification: probable IIM, subgroup: polymyositis). In contrast, even though he harboured anti-dsDNA antibodies, he did not have any lupus-related symptoms. Furthermore, there were no apparent signs for interstitial lung disease, malignancy, or cardiomyopathy by cardiac ultrasound. Figure 1. Open in new tabDownload slide (a) The short tau inversion recovery magnetic resonance image (MRI) of the thighs. High-intensity signals in the quadriceps muscles were demonstrated (white arrows). (b) Repeat MRI examination 3 months later revealed a complete resolution of abnormal findings in the thighs. Figure 1. Open in new tabDownload slide (a) The short tau inversion recovery magnetic resonance image (MRI) of the thighs. High-intensity signals in the quadriceps muscles were demonstrated (white arrows). (b) Repeat MRI examination 3 months later revealed a complete resolution of abnormal findings in the thighs. Figure 2. Open in new tabDownload slide Muscle biopsy from the right vastus lateralis muscle (haematoxylin and eosin stain) at magnifications of (a) ×200 and (b) ×400. Endomysial infiltration of mononuclear cells surrounding—but not invading—myofibers was demonstrated (white arrows). Fibre size variation, fibre rounding, and paler-staining fibre were also shown, in addition to necrotising and regenerating fibres. Figure 2. Open in new tabDownload slide Muscle biopsy from the right vastus lateralis muscle (haematoxylin and eosin stain) at magnifications of (a) ×200 and (b) ×400. Endomysial infiltration of mononuclear cells surrounding—but not invading—myofibers was demonstrated (white arrows). Fibre size variation, fibre rounding, and paler-staining fibre were also shown, in addition to necrotising and regenerating fibres. Although an adverse drug reaction of infliximab had been speculated, his muscle symptoms did not improve and his serum CK levels did not decrease in 6 weeks from the last administration of infliximab. Therefore, treatment with prednisolone 60 mg/day (1 mg/kg/day) was initiated concomitantly with azathioprine 50 mg/day. Immediately, his myalgia and muscle weakness ameliorated, and his serum CK levels and anti-DNA antibody titres returned to normal. He was discharged home and the prednisolone was tapered. A 3-months follow-up, repeat MRI revealed complete resolution of abnormal findings in his thighs (Figure 1(b)). The patient's clinical course was shown in Figure 3. At his next follow-up 1 year later, he reported no symptoms of UC or myositis while continuing treatment with prednisolone 7 mg/day and azathioprine, without the resumption of infliximab or administration of other biologic agents. Figure 3. Open in new tabDownload slide The patient’s clinical course was shown. PSL: prednisolone; AZA: azathioprine; CK: creatine kinase; dsDNA: double stranded DNA. Figure 3. Open in new tabDownload slide The patient’s clinical course was shown. PSL: prednisolone; AZA: azathioprine; CK: creatine kinase; dsDNA: double stranded DNA. Discussion This case report of TNF inhibitor-induced myositis in a patient with UC is the first in the English literature searched on PubMed to the best of these authors’ knowledge. As summarised in Table 2, for patients with rheumatic diseases and inflammatory bowel disease other than UC, 24 cases of TNF inhibitor-induced myositis have been reported [3–19]. However, in some of these reports, the diagnoses of myositis may not be definite because specific examinations, such as muscle biopsies and EMG, were not used in every case. In contrast, in the present case, a muscle biopsy, an EMG, and a MRI were performed, and their features were all compatible with polymyositis. Furthermore, the histologic findings of the present case satisfied the strict definition for polymyositis by the European Neuromuscular Centre international workshop [21]. However, the possibility of accidental complication of IIM cannot be totally excluded in this case because the myositis was treated with immunosuppressive therapy. Table 2. Reported cases of tumour necrosis factor inhibitor-induced myositis. Case Age Sex Primary diagnosis TNF inhibitor Duration of TNF inhibitor Autoantibody Anti-dsDNA Muscle biopsy Skin involvement Treatment Outcome Ref. 1 52 F RA IFX 30 m ANA, CCP, Jo-1, p-ANCA (+) (+) (-) GC Improve [6] 2 RA IFX [7] 3 52 F RA Lenercept 2.5 m (+) (+) No treatment Improve [8] 4 52 F RA IFX 9 m ANA, Jo-1 (+) (−) GC＋TAC Improve [9] 5 44 F RA ETN 6 m ANA, Jo-1 (+) (+) GC Improve [10] 6 57 F RA ADA 9 m ANA, CCP, PM-Scl (+) (+) (−) GC Improve [11] 7 40 F RA ETN 24 m ANA, RF (+) GC + RTX Relapse [12] 8 33 F RA ETN, ADA 5 m RF, CCP (+) GC + HCQ + CY Improve [12] 9 58 F RA ETN 2 m ANA, Jo-1, CCP (+) (−) GC Improve [13] 10 52 M RA ETN 17 m RF, CCP, PL-7 (+) GC Improve [14] 11 63 F RA ETN 2 m ANA, CCP, RF, SS-A, PL-12 (+) GC Improve [15] 12 45 F RA ADA 56 m ANA (+) GC Improve [16] 13 20 F RA ADA 6 m ANA, Jo-1 (+) (−) GC＋RTX＋MTX Improve [4] 14 44 F RA ADA 36 m ANA, Jo-1 (+) (+) GC + CY + RTX Improve [4] 15 57 F RA ETN 30 m ANA (+) (−) GC＋CY Death [17] 16 46 M JIA ETN, ADA 10 y (+) GC＋MTX + HCQ Improve [18] 17 29 F Arthritis ADA 3 m ANA (+) GC＋MTX + AZA Improve [12] 18 30 M AS ETN 2.5 m ANA, Jo-1 (+) (−) GC + CY Improve [4] 19 46 M AS IFX 6 m (+) (−) GC Improve [17] 20 36 M CD ADA, IFX 1 m ANA, Sm, U1-RNP (+) (+) GC＋MTX Improve [19] 21 IFX (+) [3] 22 IFX (+) [3] 23 ETN (−) [3] 24 Lenercept (−) [3] Present case 60 M UC ADA 24 m ANA, LA (+) (+) (−) GC + AZA Improve Case Age Sex Primary diagnosis TNF inhibitor Duration of TNF inhibitor Autoantibody Anti-dsDNA Muscle biopsy Skin involvement Treatment Outcome Ref. 1 52 F RA IFX 30 m ANA, CCP, Jo-1, p-ANCA (+) (+) (-) GC Improve [6] 2 RA IFX [7] 3 52 F RA Lenercept 2.5 m (+) (+) No treatment Improve [8] 4 52 F RA IFX 9 m ANA, Jo-1 (+) (−) GC＋TAC Improve [9] 5 44 F RA ETN 6 m ANA, Jo-1 (+) (+) GC Improve [10] 6 57 F RA ADA 9 m ANA, CCP, PM-Scl (+) (+) (−) GC Improve [11] 7 40 F RA ETN 24 m ANA, RF (+) GC + RTX Relapse [12] 8 33 F RA ETN, ADA 5 m RF, CCP (+) GC + HCQ + CY Improve [12] 9 58 F RA ETN 2 m ANA, Jo-1, CCP (+) (−) GC Improve [13] 10 52 M RA ETN 17 m RF, CCP, PL-7 (+) GC Improve [14] 11 63 F RA ETN 2 m ANA, CCP, RF, SS-A, PL-12 (+) GC Improve [15] 12 45 F RA ADA 56 m ANA (+) GC Improve [16] 13 20 F RA ADA 6 m ANA, Jo-1 (+) (−) GC＋RTX＋MTX Improve [4] 14 44 F RA ADA 36 m ANA, Jo-1 (+) (+) GC + CY + RTX Improve [4] 15 57 F RA ETN 30 m ANA (+) (−) GC＋CY Death [17] 16 46 M JIA ETN, ADA 10 y (+) GC＋MTX + HCQ Improve [18] 17 29 F Arthritis ADA 3 m ANA (+) GC＋MTX + AZA Improve [12] 18 30 M AS ETN 2.5 m ANA, Jo-1 (+) (−) GC + CY Improve [4] 19 46 M AS IFX 6 m (+) (−) GC Improve [17] 20 36 M CD ADA, IFX 1 m ANA, Sm, U1-RNP (+) (+) GC＋MTX Improve [19] 21 IFX (+) [3] 22 IFX (+) [3] 23 ETN (−) [3] 24 Lenercept (−) [3] Present case 60 M UC ADA 24 m ANA, LA (+) (+) (−) GC + AZA Improve ADA: adalimumab; ANA: anti-nuclear antibody; ANCA: anti-neutrophil cytoplasmic antibody; AS: ankylosing spondylitis; AZA: azathioprine; CCP: cyclic citrullinated peptide; CD: Crohn’s disease; CY: cyclophosphamide; dsDNA: double stranded DNA; ETN: etanercept; GC: glucocorticoid; HCQ: hydroxychloroquine; IFX: infliximab; JIA: juvenile idiopathic arthritis; LA: lupus anticoagulant; MTX: methotrexate; RA: rheumatoid arthritis; RF: rheumatoid factor; RTX: rituximab; TAC: tacrolimus; TNF: tumour necrosis factor; UC: ulcerative colitis; U1-RNP: U1 small nuclear ribonucleoprotein. Open in new tab Table 2. Reported cases of tumour necrosis factor inhibitor-induced myositis. Case Age Sex Primary diagnosis TNF inhibitor Duration of TNF inhibitor Autoantibody Anti-dsDNA Muscle biopsy Skin involvement Treatment Outcome Ref. 1 52 F RA IFX 30 m ANA, CCP, Jo-1, p-ANCA (+) (+) (-) GC Improve [6] 2 RA IFX [7] 3 52 F RA Lenercept 2.5 m (+) (+) No treatment Improve [8] 4 52 F RA IFX 9 m ANA, Jo-1 (+) (−) GC＋TAC Improve [9] 5 44 F RA ETN 6 m ANA, Jo-1 (+) (+) GC Improve [10] 6 57 F RA ADA 9 m ANA, CCP, PM-Scl (+) (+) (−) GC Improve [11] 7 40 F RA ETN 24 m ANA, RF (+) GC + RTX Relapse [12] 8 33 F RA ETN, ADA 5 m RF, CCP (+) GC + HCQ + CY Improve [12] 9 58 F RA ETN 2 m ANA, Jo-1, CCP (+) (−) GC Improve [13] 10 52 M RA ETN 17 m RF, CCP, PL-7 (+) GC Improve [14] 11 63 F RA ETN 2 m ANA, CCP, RF, SS-A, PL-12 (+) GC Improve [15] 12 45 F RA ADA 56 m ANA (+) GC Improve [16] 13 20 F RA ADA 6 m ANA, Jo-1 (+) (−) GC＋RTX＋MTX Improve [4] 14 44 F RA ADA 36 m ANA, Jo-1 (+) (+) GC + CY + RTX Improve [4] 15 57 F RA ETN 30 m ANA (+) (−) GC＋CY Death [17] 16 46 M JIA ETN, ADA 10 y (+) GC＋MTX + HCQ Improve [18] 17 29 F Arthritis ADA 3 m ANA (+) GC＋MTX + AZA Improve [12] 18 30 M AS ETN 2.5 m ANA, Jo-1 (+) (−) GC + CY Improve [4] 19 46 M AS IFX 6 m (+) (−) GC Improve [17] 20 36 M CD ADA, IFX 1 m ANA, Sm, U1-RNP (+) (+) GC＋MTX Improve [19] 21 IFX (+) [3] 22 IFX (+) [3] 23 ETN (−) [3] 24 Lenercept (−) [3] Present case 60 M UC ADA 24 m ANA, LA (+) (+) (−) GC + AZA Improve Case Age Sex Primary diagnosis TNF inhibitor Duration of TNF inhibitor Autoantibody Anti-dsDNA Muscle biopsy Skin involvement Treatment Outcome Ref. 1 52 F RA IFX 30 m ANA, CCP, Jo-1, p-ANCA (+) (+) (-) GC Improve [6] 2 RA IFX [7] 3 52 F RA Lenercept 2.5 m (+) (+) No treatment Improve [8] 4 52 F RA IFX 9 m ANA, Jo-1 (+) (−) GC＋TAC Improve [9] 5 44 F RA ETN 6 m ANA, Jo-1 (+) (+) GC Improve [10] 6 57 F RA ADA 9 m ANA, CCP, PM-Scl (+) (+) (−) GC Improve [11] 7 40 F RA ETN 24 m ANA, RF (+) GC + RTX Relapse [12] 8 33 F RA ETN, ADA 5 m RF, CCP (+) GC + HCQ + CY Improve [12] 9 58 F RA ETN 2 m ANA, Jo-1, CCP (+) (−) GC Improve [13] 10 52 M RA ETN 17 m RF, CCP, PL-7 (+) GC Improve [14] 11 63 F RA ETN 2 m ANA, CCP, RF, SS-A, PL-12 (+) GC Improve [15] 12 45 F RA ADA 56 m ANA (+) GC Improve [16] 13 20 F RA ADA 6 m ANA, Jo-1 (+) (−) GC＋RTX＋MTX Improve [4] 14 44 F RA ADA 36 m ANA, Jo-1 (+) (+) GC + CY + RTX Improve [4] 15 57 F RA ETN 30 m ANA (+) (−) GC＋CY Death [17] 16 46 M JIA ETN, ADA 10 y (+) GC＋MTX + HCQ Improve [18] 17 29 F Arthritis ADA 3 m ANA (+) GC＋MTX + AZA Improve [12] 18 30 M AS ETN 2.5 m ANA, Jo-1 (+) (−) GC + CY Improve [4] 19 46 M AS IFX 6 m (+) (−) GC Improve [17] 20 36 M CD ADA, IFX 1 m ANA, Sm, U1-RNP (+) (+) GC＋MTX Improve [19] 21 IFX (+) [3] 22 IFX (+) [3] 23 ETN (−) [3] 24 Lenercept (−) [3] Present case 60 M UC ADA 24 m ANA, LA (+) (+) (−) GC + AZA Improve ADA: adalimumab; ANA: anti-nuclear antibody; ANCA: anti-neutrophil cytoplasmic antibody; AS: ankylosing spondylitis; AZA: azathioprine; CCP: cyclic citrullinated peptide; CD: Crohn’s disease; CY: cyclophosphamide; dsDNA: double stranded DNA; ETN: etanercept; GC: glucocorticoid; HCQ: hydroxychloroquine; IFX: infliximab; JIA: juvenile idiopathic arthritis; LA: lupus anticoagulant; MTX: methotrexate; RA: rheumatoid arthritis; RF: rheumatoid factor; RTX: rituximab; TAC: tacrolimus; TNF: tumour necrosis factor; UC: ulcerative colitis; U1-RNP: U1 small nuclear ribonucleoprotein. Open in new tab The pathologic mechanisms of the myositis in the present case was unknown. However, these authors speculated that the infliximab-induced autoimmunity, evidenced by the induction of anti-dsDNA antibodies, played a pivotal role. As shown in Table 2, other cases have been reported of TNF inhibitor-induced myositis that coexisted with anti-dsDNA antibodies. Several mechanisms have been proposed to explain the incidence of lupus or lupus-like syndromes in patients previously treated with TNF inhibitors [22]. For example, TNF inhibitors suppress the production of Th1 cytokines, thereby driving the immune response towards the production of Th2 cytokines, such as interleukin-10 and interferon-α—a hypothesis called “cytokine shift” [22]. This shift may lead to the production of autoantibodies and a lupus-like syndrome [22]. Interestingly, it has been indicated that the specificities of anti-TNF-induced autoantibodies are not related to the patient’s underlying diagnosis and that the anti-dsDNA autoantibodies are largely restricted to IgM class of antibodies [23], as in the present case. Furthermore, anti-HMGCR autoantibodies are associated with statin-induced, immune-mediated, necrotising myopathy, and pathogenicity of anti-HMGCR was suggested [24]. In the present case, the patient was successfully treated with high-dose prednisolone after discontinuation of infliximab. However, his muscle involvement may have been ameliorated by the discontinuation of infliximab alone. In most cases, drug-induced lupus typically improves only with withdrawal of the drugs [25]. Nevertheless, in general, drug cessation should be combined with systemic immunosuppressive therapies even for drug-induced lupus when major organ involvement is present [25]. Supporting this approach, previous reports of patients with TNF inhibitor-induced myositis document that most were treated with standard immunotherapies (Table 2). In addition, myositis can cause irreversible muscle damage with treatment delay [26]. Therefore, in this case, immunosuppressive treatment with prednisolone was initiated in advance of further exacerbation of myositis. In conclusion, this report documents a case of TNF inhibitor-induced myositis with UC. If muscle symptoms develop in patients treated with TNF inhibitors, then drug-induced myositis should be considered. Patient consent A written informed consent for publication of this case report was obtained from the patient. Ethical approval Not applicable. Conflict of interest None. References Weaver AL Efficacy and safety of the anti-TNF biologic agents . Mod Rheumatol . 2004 ; 14 ( 2 ): 101 – 112 . 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TI - Tumour necrosis factor inhibitor-induced myositis in a patient with ulcerative colitis
JO - Modern Rheumatology Case Reports
DO - 10.1080/24725625.2020.1800958
DA - 2021-01-02
UR - https://www.deepdyve.com/lp/oxford-university-press/tumour-necrosis-factor-inhibitor-induced-myositis-in-a-patient-with-9Bx1QR9XW6
SP - 156
EP - 161
VL - 5
IS - 1
DP - DeepDyve
ER -