Multiple drugs

Abstract

Vulvar Crohn disease and lack of efficacy: 3 case reports In a case series, 3 patients (2 women and 1 girl) aged 15–31years were described, who developed vulvar Crohn disease (CD) during treatment with adalimumab, certolizumab pegol, mercaptopurine, prednisone, methotrexate or tacrolimus for CD. Additionally, one of the three patient exhibited lack of efficacy with adalimumab, certolizumab pegol, infliximab, triamcinolone, prednisone, clobetasol, pimecrolimus, metronidazole and mercaptopurine, while being treated for CD [duration of treatments to reactions onsets not stated; not all dosages and routes stated]. Case 1: A 31-year-old woman, who had longstanding history of CD, presented for evaluation of worsening vulvar CD. Her intestinal disease was well controlled following a colectomy and end ileostomy. However, treatment with adalimumab, certolizumab pegol, infliximab, and mercaptopurine had failed (lack of efficacy), prior to surgery. She complained of vaginal discharge, vulvar erythema, erosions, and pruritus accompanied by fissuring, cracking, and weeping of the labia majora. These complaints had been previously managed with courses of intralesional triamcinolone, oral prednisone, clobetasol 0.05% ointment, topical pimecrolimus 1% cream, and metronidazole 0.75% gel without improvement (lack of efficacy). Her cutaneous disease resolved after the initiation of oral metronidazole. But metronidazole was discontinued due to the development of peripheral neuropathy. Physical examination showed an erythematous, scaly plaque studded with pustules on the mons pubis. Oedematous, verruciform plaques of the labia majora, deep knife-cut ulcerations in the inguinal folds and intergluteal cleft, and erythema with woody induration of the medial buttocks were also noted. A vaginal examination demonstrated diffuse erythema along with copious yellow discharge. A vaginal saline wet mount revealed sheets of WBC’s. Skin culture grew methicillin-resistant Staphylococcus aureus (MRSA) and group A Streptococcus. She was started on doxycycline and rifampicin [rifampin] for MRSA treatment. She also received a short course of amoxicillin while she was awaiting the culture susceptibilities. Subsequently, she was tailored to doxycycline in combination with a topical regimen including tacrolimus 0.1% ointment, topical metronidazole 0.75% gel, mupirocin 2% ointment, and bleach baths. The treatment led to sustained improvement. At the next follow-up visit, her vulvar fissuring, pustules, and erythema resolved. The induration of the medial buttocks had softened and the swelling of the labia majora also improved. After a month-long course of doxycycline, there was continued resolution. Based on these findings and clinical presentation it was concluded that she developed vulvar CD during treatment with adalimumab, certolizumab pegol, mercaptopurine and prednisone for CD, and exhibited lack of efficacy with adalimumab, certolizumab pegol, infliximab, triamcinolone, prednisone, clobetasol, pimecrolimus, metronidazole and mercaptopurine, while being treated for CD. Case 2: A 31-year-old woman, who had CD and systemic lupus erythematous, was being treated with adalimumab and hydroxychloroquine. She presented with a 1-year history of worsening vulvar pain, oedema, pruritus and fissuring. She reported prior vulvar abscesses and cellulitis of the vulva and buttocks, which had resolved with antibiotic therapy. Physical examination showed pink, scaly plaques involving the genitocrural folds and mons pubis. The labia majora were grossly enlarged and indurated. An exophytic nodule was present on the right periclitoral skin. Rapid plasma reagin and herpes simplex virus reverse-transcription polymerase chain-reaction testing were negative. Cultures grew methicillin-susceptible Staphylococcus aureus (MSSA) and group B Streptococcus. Tests of biopsy tissues of the periclitoral skin demonstrated psoriasiform and lichenoid dermatitis, perivascular and interstitial lymphoplasmacytic infiltrate, and mixed dermal inflammation with histiocytes and giant cells, consistent with vulvar CD. Tissue cultures confirmed the presence of MSSA. She was started on cephalexin, topical metronidazole cream, and bleach baths. A compression garment was advised for the oedema. After an initial resolution with antibiotic treatment, she subsequently discontinued adalimumab because she thought the drug exacerbated her vulvar symptoms. At the follow-up visit, repeat skin cultures grew MSSA and group B Streptococcus. She was prescribed mupirocin and chlorhexidine wash and intralesional triamcinolone [Kenalog] injections were administered into the indurated areas. Despite daily Vitamin D supplementation, persistently low vitamin D levels were noted (lack of efficacy). A high-dose vitamin D supplement was started. Five months after her last dermatology appointment, the vulvar symptoms improved and she reported doing well. Based on these findings and clinical presentation it was concluded that she developed vulvar CD during treatment with adalimumab. Case 3: A 15-year-old woman, who had well-controlled CD being treated with infliximab, presented with a 1-year history of persistent erythema, oedema, and desquamative inflammatory vaginitis (DIV) with discharge from the perianal and vulvar skin. Physical examination revealed oedematous, lichenified plaques involving the labia majora and mons pubis. She was initiated on SC methotrexate 25mg injection every week, with significant disease progression despite compliance and continued treatment with infliximab. The methotrexate was stopped and she was treated with weekly bleach baths, serial intralesional triamcinolone, topical treatments including clobetasol ointment mixed with tacrolimus 0.1% ointment and metronidazole 1% cream, leading to short-term improvement. Subsequently, she developed an abscess of the left labium majus that grew methicillin-susceptible Staphylococcus aureus (MSSA) on tissue culture. Magnetic resonance enterography excluded fistulizing CD. Her disease course was complicated by multiple MSSA as well as group A streptococcal infections. She underwent incision and drainage and treated with weekly bleach baths, intermittent courses of oral metronidazole, topical metronidazole cream mixed with clobetasol and tacrolimus, and serial intralesional triamcinolone. With the discontinuation of oral metronidazole, flaring was consistently noted. Persistently elevated fecal calprotectin, rising inflammatory markers and worsening gastrointestinal symptoms prompted a switch in therapy to ustekinumab. Nutritional assessment revealed vitamin D deficiency. The deficiency was corrected with supplementation, resulting in significant improvement in DIV with decreased discharge, but no change in vulvar CD. Based on these findings and clinical presentation it was concluded that she developed vulvar CD during treatment with methotrexate, tacrolimus and infliximab.