Hyper-IgE syndrome in an 11 year old female presenting with acneiform rash.

Hyper-IgE (HIES) is a rare, primary immunodeficiency characterised by eczema, recurrent staphylococcal infections, pneumonia, increased serum IgE and eosinophilia. We present the case of an 11-year-old girl presenting to dermatology with an acneiform facial rash and associated bacterial lymphadenitis. History was significant for otitis media, primary tooth retention, low impact wrist fracture, infantile acne and an absence of eczema or pneumonia. Investigations demonstrated mildly elevated IgE, normal eosinophils but positivity for a STAT3 gene mutation-thus representing a case of HIES presenting as an acneiform facial rash with absence of other primary immunological features.

Apalutamide-Induced Toxic Epidermal Necrolysis in a Caucasian Patient with Metastatic Castration-Sensitive Prostate Cancer: A Case Report and Review of the Literature.

Apalutamide is a novel nonsteroidal androgen receptor inhibitor that has been shown to improve outcomes for patients with nonmetastatic castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer when combined with androgen deprivation therapy. Apalutamide-induced skin rash occurred commonly in clinical trials, with 23.8-27.1% of patients experiencing a rash of any grade, and 5.2-6.3% experiencing a rash of grade three or higher. There were no cases of severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) reported in clinical trials; however, there are rare cases reported in the literature with the majority occurring in Asian patients. An 83-year-old Caucasian male was commenced on apalutamide, combined with degarelix, for the management of metastatic castration-sensitive prostate cancer. During week five of apalutamide treatment, the patient developed a widespread erythematous maculopapular rash. On presentation, the rash affected 80% of his body surface area (BSA) and a diagnosis of a severe cutaneous drug eruption was made. He was commenced on methylprednisolone (MP) therapy. Despite 5 days of MP, the rash continued to deteriorate involving 95% of his BSA. Nikolsky's sign was positive. A diagnosis of overlap SJS/TEN was made, supported by skin biopsy. His SCORTEN score was three. He was then commenced on intravenous immunoglobulin and transferred to the intensive care unit. Over the coming days, the rash began to stabilise, and his steroid dose was weaned. He was discharged from hospital 38 days after rash onset. We report the first suggested case of apalutamide-induced SJS/TEN in a Caucasian patient. We discuss other cases of apalutamide-induced SCARs reported in the literature. Risk factors seem to include low body weight and Japanese race, as well as short time to onset of rash.

Biological and JAK inhibitor therapy outcomes for severe psoriasis in trisomy 21.

Little is known about biological outcomes for severe psoriasis in trisomy 21 (T21). Our aim was to review outcomes of patients with T21 and severe psoriasis treated with biologic or Janus kinase inhibitors (JAKi). Information on demographics, co-morbidities, and therapeutic responses was retrospectively collated. Twenty-one patients were identified (mean age 24.7 years). Ninety percent (18/20) of TNFα inhibitor trials failed. Almost two-thirds (7/11) of patients achieved an adequate response with ustekinumab. All three patients treated with tofacitinib achieved an adequate response following at least three biologic failures. The mean number of biologic/JAKi therapies received was 2.1 with overall survival of 36%. Eighty-one percent (17/21) of patients required conversion from their index biologic treatment due to failure. In patients with T21 and severe psoriasis, failure of TNFα inhibition is common and ustekinumab therapy should be considered as first-line therapy. The role of JAKi is emerging.

Systemic evaluation of cutaneous sarcoidosis: 15-year dermatology experience at University Hospital Limerick.

Sarcoidosis is a multisystem granulomatous disease that can affect almost any organ including the skin, liver, ocular, cardiac, renal, nervous, musculoskeletal and endocrine systems. Systemic evaluation is indicated in all patients diagnosed with cutaneous sarcoidosis, as it is associated with asymptomatic systemic disease in 30%-40% of patients. Guidelines recommend that patients diagnosed with sarcoidosis undergo baseline and surveillance investigations including full blood count (FBC), renal and liver profile, Vitamin D, serum calcium, electrocardiography (ECG), chest radiography, pulmonary function tests (PFTs) and ophthalmology examination to assess for systemic involvement. Recommendations for surveillance monitoring vary on interval duration but include regular FBC, biochemistry, chest radiography and PFTs, with additional investigations and prompt referral to respective specialties as indicated.. We conducted a retrospective analysis to evaluate extracutaneous involvement and systemic evaluation of patients diagnosed with cutaneous sarcoidosis during the period 2004-2020, and compared our findings with international guidelines. Cutaneous manifestation was the primary presentation for 67% of the patients (12 of 18), an extracutaneous disease subsequently developed in 67% (8 of 12) of these patients. Baseline investigations included chest radiography (94%; 17 of 18), PFTs (39%; 7 of 18), FBC (94% (17 of 18), renal profile (89%; 16 of 18), liver function tests (83%; 15 of 18) and serum calcium (89%; 16 of 18); ECG was performed for 4 (25%) of 16 patients. No Vitamin D levels were recorded. Specialist referral was required for 89% (16 of 18); of these 16 patients, 94% (15 of 16) required referral to the Respiratory Medicine department, 69% (11 of 16) to Ophthalmology and 19% (3 of 16) to Nephrology. The results highlight the importance of a structured protocol for the systemic evaluation of patients diagnosed with cutaneous sarcoidosis. We subsequently developed a baseline and surveillance protocol for the assessment of extracutaneous disease in patients at University Hospital Limerick.

Metastatic melanoma in the Mid-West of Ireland: a retrospective review.

BACKGROUND: Melanoma is the fifth most common invasive cancer in Ireland, and incidence is increasing. Metastatic melanoma has been associated with poor overall survival historically. New systemic anti-cancer treatment (SACT) options for advanced melanoma have emerged in the last decade, and outcomes are improving. AIMS: The aim of our study was to assess the incidence and clinicopathological features of metastatic melanoma in our centre, and subsequent treatment with SACT. METHODS: We analysed retrospectively patients with metastatic melanoma in the Mid-West of Ireland, over a 6-year period (2014-2019). RESULTS: In 6 years, a total of 620 patients were diagnosed with melanoma, 28 (5%) had metastatic or unresectable disease at diagnosis. Mean age at primary diagnosis was 64.5 years (range 24-90 years) and 20 (71%) were male. Median Breslow depth was 4.3 mm (mean 5.5 mm, SD ± 4.4 mm). Thirteen patients (46%) had metastases at initial presentation. Fifteen (53%) received systemic treatment in the regional cancer centre. Of 13 who did not have systemic treatment, 8 had radiological and clinical surveillance, 3 declined further treatment or surveillance and 2 were lost to follow-up. Eleven patients died from the disease with median overall survival of 1.5 years (SD ± 1.3 years). CONCLUSION: Patients with metastatic melanoma commonly had metastases at the time of first presentation. Just over half of patients with metastatic melanoma received SACT. Early detection of melanoma is key. Further research on factors involved in late presentation, and those precluding systemic treatment, may contribute to improved outcomes in advanced melanoma.