BI22: A three-patient case series: methotrexate-induced nasal septal perforation, mucositis and widespread ulceration

A. Shah, S. August, S. Jain and C. Morgan

University Hospitals Dorset, Poole, UK

We present a case series of three patients on long-term methotrexate (MTX) for rheumatoid arthritis each of whom developed toxicities with delayed presentation. A 76-year-old female presented to dermatology with painful purpuric erosions affecting her lower legs. Over 12 months this became increasingly painful, widespread and ulcerating. The clinical picture and biopsy were in keeping with nodular vasculitis and the patient was started on high-dose prednisolone. After 4 weeks the patient presented with purpuric nodules, multiple new areas of ulceration associated with erythema, pain and oedema affecting the lower legs (preventing mobilization) and right elbow. A septal perforation was also noted. The patient developed flu-like symptoms so MTX was stopped for 3 weeks. When reviewed there was significant resolution of the areas of ulceration and pain. We continued to withhold MTX. After a further 4 weeks there has been almost total resolution of the skin in all affected areas. We concluded that the ulceration was caused by MTX and may have been triggered by the introduction of a proton pump inhibitor (PPI) to the patient’s medication. A 65-year-old was admitted for severe ulceration affecting the oral mucosa and lower legs. The oral ulceration worsened over 4 weeks. The patient had widespread haemorrhagic crusting and ulceration affecting the oral cavity. It was discovered that despite worsening renal function the patient’s dose of MTX was not reduced. The oral ulceration improved once MTX was stopped and folinic acid given. An 87-year-old was admitted owing to dehydration, confusion and severe mucositis. One week prior to the ulceration starting, the patient was treated with ciprofloxacin for a urinary tract infection. The oral ulceration improved with triple-therapy mouthwash and the withdrawal of MTX. Case reports and pharmacy guidelines show the ciprofloxacin can induce MTX toxicity. MTX is a dihydrofolate reductase inhibitor used commonly as a disease-modifying antirheumatic drug and in many dermatological conditions. The ability of MTX to inhibit cellular proliferation could be the mechanism by which the normal regeneration of the epithelium is inhibited, predisposing patients to septal necrosis and perforation, as well as ulceration at other sites. Given the widespread and common use of MTX in multiple inflammatory conditions this is an important side-effect to be aware of. Such effects can be caused by PPIs, as well as by some commonly used antibiotics.