Jeimy Samira, Basharat Pari, Lovegrove Fiona
1Division of Clinical Immunology and Allergy, Department of Medicine, Western University, London, ON Canada.
4Division of Clinical Immunology and Allergy, St. Joseph's Health Care London, Room B3-112, 268 Grosvenor Street, London, ON N6A 4V2 Canada.
Allergy Asthma Clin Immunol. 2019 Jan 17;15:4. doi: 10.1186/s13223-019-0319-4. eCollection 2019.
Omalizumab is a humanized monoclonal antibody widely used for treatment of persistent allergic asthma and antihistamine-refractory chronic urticaria. Immediate adverse events to omalizumab are well characterized. Delayed anaphylactoid and serum sickness-like reactions have also been described; however, their relationship to the drug remains uncertain, and the frequency is unknown.
We present a case of a 59-year old female who developed amyopathic dermatomyositis (DM) after receiving omalizumab infusions for steroid-refractory severe asthma. After 6 months of omalizumab, the patient developed an erythematous, intensely pruritic cutaneous eruption. Skin biopsy indicated nonspecific features of dermatitis. However, neither topical corticosteroids nor gabapentin and maximal doses of multiple antihistamines gave her relief. On follow-up clinical exam 8 months later, she had classic cutaneous features of dermatomyositis, with confirmatory repeat skin biopsy. Laboratory investigations revealed negative myositis specific antibodies, positive antinuclear antibody, and negative anti-histone antibodies. Creatine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase levels and C-reactive protein were also within normal limits. These findings supported the clinical impression of amyopathic DM. The patient's symptoms improved with oral corticosteroid therapy. A malignancy screen was negative. There was no evidence of end organ dysfunction.
Dermatomyositis is not a known adverse effect of omalizumab therapy. DM has a low incidence, but potentially life threatening consequences. Amyopathic DM may represent up to 21% of cases of DM, with similar risks of malignancy and end organ dysfunction. DM has been associated with biologic therapy. Using the Naranjo adverse drug reaction (ADR) probability scale, our patient had a "probable" omalizumab related ADR. A more likely explanation is that the patient had underlying DM that remained occult due to chronic corticosteroid therapy. Our case highlights the need for clinical vigilance and maintenance of a broad differential when patients on biologic therapies present with cutaneous eruptions. In our patient, the cutaneous clinical features of DM became pronounced over serial assessments. Laboratory markers may be deceptively normal, as in amyotrophic DM, or confounded by ongoing corticosteroid therapy. There are important clinical implications of prompt diagnosis, given the association of DM with end organ disease including interstitial lung disease, and possible concomitant malignancy.
奥马珠单抗是一种人源化单克隆抗体,广泛用于治疗持续性过敏性哮喘和抗组胺药难治性慢性荨麻疹。奥马珠单抗的即刻不良事件已得到充分表征。也有关于迟发性类过敏反应和血清病样反应的描述;然而,它们与该药物的关系仍不确定,且发生率未知。
我们报告一例59岁女性,在接受奥马珠单抗输注治疗类固醇难治性重度哮喘后发生无肌病性皮肌炎(DM)。使用奥马珠单抗6个月后,患者出现红斑、剧烈瘙痒的皮疹。皮肤活检显示为非特异性皮炎特征。然而,局部使用皮质类固醇、加巴喷丁以及多种抗组胺药的最大剂量均未能缓解她的症状。8个月后的随访临床检查中,她出现了皮肌炎的典型皮肤特征,再次皮肤活检得以确诊。实验室检查显示肌炎特异性抗体阴性、抗核抗体阳性、抗组蛋白抗体阴性。肌酸激酶、乳酸脱氢酶、天冬氨酸转氨酶、丙氨酸转氨酶水平及C反应蛋白也均在正常范围内。这些发现支持了无肌病性DM的临床诊断。患者症状经口服皮质类固醇治疗后有所改善。恶性肿瘤筛查结果为阴性。无终末器官功能障碍的证据。
皮肌炎并非奥马珠单抗治疗已知的不良反应。DM发病率较低,但可能危及生命。无肌病性DM可能占DM病例的21%,具有相似的恶性肿瘤和终末器官功能障碍风险。DM与生物治疗相关。使用Naranjo药物不良反应(ADR)概率量表,我们的患者发生了“很可能”与奥马珠单抗相关的ADR。更有可能的解释是,患者存在潜在的DM,但由于长期使用皮质类固醇治疗而隐匿未现。我们的病例强调,当接受生物治疗的患者出现皮肤皮疹时,临床需要保持警惕并进行全面鉴别诊断。在我们的患者中,DM的皮肤临床特征在系列评估中变得明显。实验室指标可能看似正常,如在无肌病性DM中,或因持续的皮质类固醇治疗而混淆。鉴于DM与包括间质性肺病在内的终末器官疾病以及可能伴发的恶性肿瘤相关,及时诊断具有重要的临床意义。