Rheumatology, Osmangazi University, 1 Anesthesia and Intensive Care Unit, Osmangazi University, Eskiþehir, Turkey.
Correspondence to: C. Korkmaz. E-mail: ckorkmaz{at}ogu.edu.tr
SIR, Respiratory complications can be seen in the course of dermatomyositis (DM), but alveolar hypoventilation due to respiratory muscle weakness has only been infrequently reported [1, 2]. Alveolar hypoventilation can be resistant to conventional agents, which may result in either death or dependence on home mechanical ventilation [2, 3].
We present a patient with DM with alveolar hypoventilation who failed to respond to a combined immunosuppressive treatment. The initiation of anti-tumour necrosis factor-alpha (anti-TNF-) resulted in improvement in her ventilatory insufficiency.
A 19-yr-old girl was admitted to hospital with a 1-month history of having difficulty in swallowing apart from dysphonia. Physical examination disclosed heliotrope rashes and periungual erythema. Her proximal muscle power was 2/5. Her erythrocyte sedimentation rate (ESR) was 28 mm/h. Serum levels of muscle enzymes were increased: creatinine kinase (CK) 3050 U/l (normal 16190), lactate dehydrogenase (LDH) 1257 U/l (normal 240480), aspartate aminotransferase (AST) 284 U/l (normal 040), alanine aminotransferase (ALT) 75 U/l (normal 040). Antinuclear antibodies (ANA), anti-DNA and antibodies to extractable nuclear antigen were all negative. Electroneuromyography and muscle biopsy were consistent with DM.
The patient was started on an initial dose of prednisolone 60 mg/day, methotrexate (MTX) 10 mg weekly and hydroxychloroquine 400 mg/day following a diagnosis of DM. After 4 weeks, the dosage of prednisolone was reduced by 57.5 mg decrements every 10 days down to a dosage of 15 mg a day. Seven weeks later the muscle weakness, dysphonia and difficulty in swallowing had not improved, although the levels of CK and LDH had decreased to 587 and 1060 U/l respectively. Intravenous immunoglobulin (IVIG) was administered at a dose of 400 mg/kg/day for five consecutive days and the dosage of MTX was increased to 15 mg weekly. Before the sixth course of IVIG, the patient had to be hospitalized due to polyarthritis, rashes, increased dysphonia and difficulty in swallowing. Cyclosporin A was added to MTX (17.5 mg weekly) in dosages of 200 mg/day. IVIG was discontinued after six courses. After 1 month, the patient was readmitted to hospital due to hypoventilation, cyanosis and increased dysphonia while still receiving MTX, cyclosporin, prednisolone and hydroxychloroquine. Arterial blood gases at rest were as follows: PO2 40 mmHg, PCO2 41 mmHg, pH 7 39. The patients was intubated and mechanically ventilated for the ineffective ventilation. Investigations at this stage demonstrated an ESR of 33 mm/h, CK 375 U/l, LDH 827 U/l, AST 83 U/l and ALT 20 U/l. She was treated with intravenous pulses of methylprednisolone (1 g/day) for 3 days in succession, which was followed by a dosage of 1 mg/kg/day intravenously afterwards. MTX was also given 15 mg weekly intravenously. As we did not observe any improvement in her clinical conditions or laboratory findings, infliximab (Remicade) (8 mg/kg), infusions given at 0, 2 and 6 weeks, had to be added to the aforementioned agents. After 8 days, spontaneous respiration reappeared and the need for mechanical ventilation decreased. She was extubated on the thirteenth day of the treatment of infliximab. Consequently, she was mobile with support. She resumed eating, starting with liquids on the sixteenth day. Prednisolone was decreased to 15 mg within 8 weeks and azathioprine was added to oral MTX (17.5 mg) and hydroxychloroquine (400 mg/day) in dosages of 50 mg/day with the exclusion of cyclosporin. The patient was feeling well by the fourth infusion of infliximab. She was able to swallow with no difficulty, with the total disappearance of dysphonia. Her muscle power was 23/5. Arterial blood gases at rest were: PO2 85 mmHg, PCO2 36 mmHg, pH 7 44.
Although there are some patients with alveolar hypoventilation due to DM who may respond to steroids [1], it may still result in the death of the patient or in dependency on permanent home mechanical ventilation despite conventional immunosuppressive treatments [2, 3]. Our patient was resistant to conventional agents including MTX, IVIG, cyclosporin and prednisolone. After the initiation of infliximab, her clinical condition improved rapidly. Although we could not exclude the possibility that high-dose steroids might have contributed to such a result, anti-TNF- treatment might also have played a major role in resolution of alveolar hypoventilation in our case. Selva-OCallaghan et al. [2] reported three patients with inflammatory myopathy and respiratory failure due to muscle weakness who did not respond to an immunosuppressive treatment inclusive of high-dose prednisolone. The muscle weakness and dermatological findings in our patient had also resolved mildly while she was on a high-dose prednisolone at the onset of the disease. We therefore conclude that some patients with alveolar hypoventilation due to DM may not benefit from immunosuppressives inclusive of steroids.
Infliximab is an IgG1 chimeric anti-TNF- monoclonal antibody with proven efficacy and safety in rheumatoid arthritis and Crohn's disease [4, 5]. Several studies have indicated a prominent role for TNF-
and interleukin-1 (IL-1) in the pathogenesis of polymyositis and DM [6, 7]. Therefore, blocking of TNF-
appears to be an alternative rational therapy for resistant DM and polymyositis, especially as endogenous TNF contributes to the subsequent induction of IL-1 [8]. Anti-TNF-
treatment works either in DM and polymyositis patients with resistance to conventional agents or as the first-line therapy [9, 10].
In conclusion, anti-TNF- treatment resulted in improvement in alveolar hypoventilation and difficulty in swallowing due to DM. We suggest that anti-TNF-
treatment is a safe, effective therapy giving rapid improvement of alveolar hypoventilation, dysphonia and difficulty in swallowing due to DM.
The patient has given consent for this material to appear in Rheumatology.
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The authors have declared no conflicts of interest.
References
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