What is the recommended treatment for anti‑OJ (anti‑isoleucyl‑tRNA‑synthetase) myositis presenting with skin ulceration?

Treatment of Anti-OJ Myositis with Skin Ulcers

For anti-OJ myositis presenting with skin ulceration, initiate high-dose intravenous methylprednisolone (15-30 mg/kg/dose for 3 consecutive days) followed by oral prednisolone (1-2 mg/kg/day) combined with subcutaneous methotrexate (15-20 mg/m²/week), and add intravenous immunoglobulin (IVIG) given the extensive ulcerative skin disease, which represents severe disease requiring treatment intensification. 1

Understanding Anti-OJ Antibody Context

• Anti-OJ (anti-isoleucyl-tRNA synthetase) is one of the antisynthetase antibodies that defines antisynthetase syndrome, characterized by myositis, interstitial lung disease, arthritis, Raynaud's phenomenon, mechanic's hands, and fever 2, 3
• Anti-OJ positive patients typically show good prognosis and favorable response to glucocorticoid therapy compared to other antisynthetase antibodies, and notably lack Raynaud's phenomenon and sclerodactyly 4
• The presence of skin ulceration in your patient indicates severe disease requiring aggressive upfront treatment 1

First-Line Treatment Protocol

Immediate Corticosteroid Therapy

• Start with intravenous methylprednisolone pulse therapy at 15-30 mg/kg/dose (maximum 1000 mg) for 3 consecutive days, which is FDA-approved for dermatomyositis 5, 1
• Transition to oral prednisolone 1-2 mg/kg/day (typically 60-80 mg daily for adults) after completing pulse therapy 1, 6
• Intravenous administration is preferred initially when there are concerns about absorption, which is relevant given the severe skin disease 1

Concurrent Steroid-Sparing Agent

• Initiate methotrexate 15-20 mg/m²/week (maximum 40 mg/week) via subcutaneous route at disease onset, as subcutaneous administration provides superior absorption compared to oral dosing 1, 6
• The combination of methotrexate and prednisolone has superior safety profiles compared to prednisolone alone and leads to better disease control 1

Treatment Intensification for Severe Disease

• Add IVIG immediately given the extensive ulcerative skin disease, which qualifies as severe disease requiring upfront intensification 1
• IVIG is particularly useful when skin features are prominent and is recommended as an adjunct for resistant disease 1
• Consider adding mycophenolate mofetil (MMF) as it is useful therapy for both muscle and skin disease 1, 7

Critical Safety Monitoring

Baseline Cardiac Evaluation

• Obtain baseline troponin I and electrocardiography before initiating treatment, as myocarditis occurs in approximately 20% of severe myositis cases 6
• If troponin is elevated or clinical symptoms suggest cardiac involvement, obtain cardiac MRI immediately 6
• Normal cardiac enzymes do not completely exclude myocarditis 6

Pulmonary Assessment

• Perform immediate pulmonary evaluation with high-resolution CT and pulmonary function tests, as anti-OJ is an antisynthetase antibody associated with interstitial lung disease 2, 4
• Previous reports show anti-OJ patients may present with ILD that responds well to glucocorticoid therapy 4

Baseline Laboratory Monitoring

• Check creatine kinase (CK), lactate dehydrogenase (LDH), AST, ALT, and aldolase for baseline muscle enzyme levels 1
• Obtain complete blood count and comprehensive metabolic panel before starting methotrexate 6, 7

Treatment Response Assessment and Escalation

12-Week Evaluation

• Assess clinical response at 12 weeks by monitoring muscle strength using validated tools (Childhood Myositis Assessment Scale or Manual Muscle Test), skin disease activity, CK levels, and inflammatory markers 1, 6
• Verify medication adherence and tolerance before escalating therapy 1, 6
• MRI with T1-weighted, T2-weighted, and fat suppression sequences can objectively monitor treatment response 6

Management of Inadequate Response

• If inadequate response despite adherence, intensify treatment by adding or changing to other medications including cyclophosphamide, rituximab, or anti-TNF agents (infliximab or adalimumab preferred over etanercept) 1
• For methotrexate intolerance, switch to mycophenolate mofetil or cyclosporine A 1, 7
• Consider intravenous cyclophosphamide for patients with severe disease such as major organ involvement or extensive ulcerative skin disease 1
• Rituximab can be considered as adjunctive therapy for refractory disease, but clinicians should be aware it can take up to 26 weeks to work 1

Corticosteroid Tapering Strategy

• Begin tapering corticosteroid dose as the patient shows clinical improvement 1
• Continue methotrexate (or alternative DMARD) throughout the taper 1
• Consideration may be given to withdrawing treatment if a patient has been off steroids and in remission on methotrexate for a minimum of 1 year 1

Essential Supportive Measures

Skin Protection and Topical Therapy

• Rigorous sun protection with SPF 50+ sunscreen and physical barriers is paramount, as UV light exposure may trigger disease flares 6, 7
• Topical tacrolimus 0.1% or topical steroids may help localized skin disease, particularly for symptomatic redness or itching, but ongoing skin disease reflects ongoing systemic disease and should be treated by increasing systemic immunosuppression 1, 7

Infection Prophylaxis and Bone Protection

• Provide calcium and vitamin D supplementation to prevent corticosteroid-induced osteoporosis 6
• Consider Pneumocystis jirovecii pneumonia (PCP) prophylaxis given the high-dose immunosuppression 6

Physical Therapy

• Implement a supervised physiotherapy program to restore muscle strength, monitored by a physiotherapist as part of a multidisciplinary team 1
• Exercise should be safe and appropriate, introduced during the remission phase rather than during active inflammation 6

Common Pitfalls to Avoid

• Do not delay treatment intensification: Extensive ulcerative skin disease qualifies as severe disease requiring upfront aggressive therapy, not a stepwise approach 1
• Do not rely on topical therapy alone: Ongoing skin disease, including ulceration, reflects ongoing systemic disease and requires increased systemic immunosuppression 1
• Do not overlook cardiac involvement: Always obtain baseline cardiac evaluation before treatment, as myocarditis can be life-threatening 6
• Do not forget pulmonary screening: Anti-OJ is an antisynthetase antibody with ILD risk requiring immediate pulmonary assessment 2, 4
• Do not use oral methotrexate: Subcutaneous administration provides superior absorption and should be preferred 1, 6