Scleroderma Secondary to Pembrolizumab: A Case Report and Review of 19 Cases of Anti-PD-1-Induced Scleroderma.

Immune checkpoint inhibitors are increasingly being used to treat various malignancies. Despite their efficacy, they are known to potentially cause immune-related adverse effects, including dermatological manifestations. A rare cutaneous immune-related adverse effect is scleroderma, which has been reported to occur with anti-programmed cell death-1 (PD-1) agents such as pembrolizumab and nivolumab. This may present with skin tightening and hardening at any point during or after immunotherapy. We present the case of a 54-year-old Caucasian woman who, following 16 doses of pembrolizumab for breast cancer, developed clinical features of scleroderma confirmed on histology. She was initially treated with oral corticosteroids, followed by oral psoralen-UVA, with poor response, but eventually improved with methotrexate. A literature review revealed 12 other cases of scleroderma following pembrolizumab treatment and 6 cases of scleroderma following nivolumab treatment. Males and females were both affected, and their ages ranged from 33 to 81 years. Scleroderma developed at different stages of pembrolizumab or nivolumab therapy. Although scleroderma is not commonly drug-induced, anti-PD-1 agents may be a rare cause and it is important to elicit an accurate drug history, including immunotherapy, in such cases.

Cutaneous Melanoma More Likely to Be Invasive in Fairer Skin Phototypes: A Retrospective Observational Study.

Fitzpatrick skin phototype is one of the factors determining melanoma development, with fairer skin phototypes I and II known to be associated with a higher risk. This study aimed to identify any associations between skin phototype and the histologic subtype, Breslow's thickness, and the site of melanoma. Patients diagnosed with melanoma for over an 18-month period were included. Data were gathered from the Malta National Cancer Registry. There were 167 registered cutaneous melanoma patients, of which 135 were included in the study. Melanomas in patients with skin phototypes I and II were more likely to be invasive than in situ when compared to patients with skin phototypes III and IV (P = 0.00027). There was also an association between skin phototype and histologic type of melanoma (P = 0.005), with melanoma in situ being the most common subtype in patients with skin type III. This study confirms that fairer skin phototypes have an increased risk of melanoma. It also shows that in our population, melanoma in skin phototypes I and II is more likely to be invasive rather than in situ compared to melanoma in darker skin phototypes. Further studies are required to confirm these findings and identify possible reasons.

A novel SPINK5 donor splice site variant in a child with Netherton syndrome.

BACKGROUND: Netherton syndrome (NS) is a genodermatosis caused by loss-of-function mutations in SPINK5, resulting in aberrant LEKTI expression. METHOD: Next-generation sequencing of SPINK5 (NM_001127698.1) was carried out and functional studies were performed by immunofluorescence microscopy of a lesional skin biopsy using anti-LEKTI antibodies. RESULTS: We describe a novel SPINK5 likely pathogenic donor splice site variant (NM_001127698.1:c.2015+5G>A) in a patient with NS and confirm its functional significance by demonstrating complete loss of LEKTI expression in lesional skin by immunofluorescence analysis. CONCLUSION: The 2015+5G>A is a novel, likely pathogenic variant in NS. Herein we review and assimilate documented SPINK5 pathogenic variants and discuss possible genotype-phenotype associations in NS.

The Antibiotic Susceptibility Profile of Cutibacterium Acnes in Maltese Patients with Acne.

BACKGROUND: Antibiotics have been widely used for the management of acne vulgaris, which has led to increased resistance of Cutibacterium acnes (C. acnes). OBJECTIVES: We sought to determine the susceptibility profile of C. acnes, isolated from patients with acne, to different prescribed antibiotics and compare our findings with global data. The relationship between antibiotic resistance and sex, age, acne severity, presence of any affected siblings, disease duration, and previous antimicrobial treatment was also investigated. METHODS: Samples were collected from randomly selected pustular acne lesions of patients attending the Dermatology Outpatients Clinic at Sir Paul Boffa Hospital in Floriana, Malta. Samples were inoculated and incubated in anaerobic conditions until 100 cultured C. acnes samples were obtained. Antibiotic susceptibility testing was then performed using azithromycin, clindamycin, doxycycline, minocycline, tetracycline, and trimethoprim/sulfamethoxazole using the agar dilution method. RESULTS: The highest resistance was observed to azithromycin (18%) followed by clindamycin (16%). Resistance to doxycycline and tetracycline was only found in two percent of the isolates and there was no resistance to trimethoprim/sulfamethoxazole and minocycline. Resistance to azithromycin and clindamycin was associated with acne severity (p=0.01 and p=0.03). Resistance to clindamycin was also statistically significantly higher in patients with a history of antibiotic therapy or concurrent antibiotic therapy during the study (p=0.04). CONCLUSION: To our knowledge, this is the first study documenting the susceptibility of C. acnes isolates to different antibiotics in Malta. Future research is needed to determine the clinical significance of antibiotic resistance of C. acnes.

Continuous Positive Airway Pressure: Is it a route for infection in those with Obstructive Sleep Apnoea?

INTRODUCTION: Continuous positive airway pressure (CPAP) is the standard treatment for obstructive sleep apnoea (OSA), with limited data about the prevalence of respiratory infections and microbial colonization in these patients. OBJECTIVES: The aim of this study was to determine if CPAP use is associated with respiratory infections and to identify the organisms that colonize or infect these patients. METHOD: A retrospective, case-controlled study in patients diagnosed with OSA was carried out. 137 patients were recruited and interviewed using a questionnaire. A nasal swab was taken from each patient. Patients using CPAP machines had swabs taken from masks and humidifiers. RESULTS: 66 (48.2%) patients received CPAP treatment with 60.6% of them having a heated humidifier. 78.8% were male, with the majority using a full face mask (63.6%). No significant difference was seen in the prevalence of rhinosinusitis, lower respiratory tract infections and hospital admissions for pneumonia between CPAP and non-CPAP treated patients. The presence of a humidifier did not influence the prevalence of infections. Commensal flora was predominantly cultured from nasal swabs from both patient groups. Coagulase Negative Staphylococci and Diphtheroids were the main organisms cultured from masks and humidifiers respectively. CONCLUSIONS: This study shows that the use of CPAP, choice of mask and humidifier have no significant impact on the prevalence of infections and micro-organisms isolated. This is very reassuring to the physician prescribing CPAP therapy and users.

Penile Granuloma Annulare.

A 50-year-old man presented to the genitourinary medicine clinic with a 3-year history of skin-colored circular papules over the shaft and glans of the penis. There were multiple lesions that were initially small, around 0.3 cm in diameter, and gradually enlarged. Physical examination revealed five nodules over the glans and shaft of the penis, with the largest lesion measuring 3×1 cm over the lateral aspect of the shaft (Figure 1). There were no similar lesions elsewhere. There was no lymphadenopathy and the rest of the examination was unremarkable. The patient complained of discomfort during sexual intercourse but the lesions were otherwise asymptomatic and nontender. There was no history of trauma to the area and no dermatological history. He had had the same sexual partner for the past 22 years, no significant medical history, and was not taking any medication. He was a smoker with a 32-pack-year history. His family history did not include any dermatological diseases. His father was diagnosed with type II diabetes at 65 years of age and his mother had hypertension since age 60 years. He had consulted his general practitioner regarding the penile eruption a year earlier and was treated for a presumed fungal infection with clotrimazole cream for 1 month with no effect. Results from genitourinary investigations for sexually transmitted diseases including syphilis were all negative.

Rare case of dermonecrosis caused by a recluse spider bite in Europe.

Spider poisoning is rare in Europe, with very few reported cases in the literature. Recluse spider (genus Loxosceles) bites may lead to cutaneous and systemic manifestations known as loxoscelism. We report the second known case of spider bite poisoning in Malta caused by Loxosceles rufescens (Mediterranean recluse spider). A young adult female presented with localised erythema and pain on her left thigh after a witnessed spider bite. Over a few days, the area developed features of dermonecrosis together with systemic symptoms, including fever, fatigue and a generalised erythematous eruption. She was managed by a multidisciplinary team and the systemic symptoms resolved within 6 days, while the skin lesion healed with scarring within 2 months. A recluse spider bite should be considered in patients with dermonecrosis. Although spider bite poisoning is uncommon in Europe, it is important to diagnose and manage it appropriately since it could lead to potentially serious sequelae.

Chronic kidney disease referral practices among non-nephrology specialists: A single-centre experience.

BACKGROUND: Early referral of CKD patients to nephrology teams (NT) is vital to identify patients most likely to progress, delay decline of excretory function, and provide planned RRT. Unfortunately, many are still being referred late. METHODS: We conducted a retrospective analysis to investigate referral rates, predictors of non-referral, and performed urine investigations in hospitalised CKD patients. RESULTS: Out of 388 patients studied, 5.6%, 11.4%, and 16.4% in CKD3A, 3B, and 4+5, respectively, were referred to an NT upon discharge (CKD3A vs. CKD4+5, p=0.016). For every additional year of age, the odds of being referred decreased by 5% (OR: 0.95, CI: 0.92-0.98, p=0.003). Patients were more likely to be referred to an NT if they were males (OR: 2.31, CI: 1.09-4.90, p=0.029) and having reached CKD 4+5 (OR: 3.99, CI: 1.58-10.10, p=0.003). Only 28.8%, 43.9%, and 50.7% of patients with CKD3A, 3B, and 4+5 were followed up with urine investigations after discharge (p=0.001). CKD stage 3B (OR: 3.54, CI: 1.23-10.19, p=0.019), CKD stage 4+5 (OR: 6.06, CI: 1.69-21.67, p=0.006), DM (OR: 6.28, CI: 2.38-16.58, p<0.0001), and having been referred to a NT (OR: 20.95, CI: 3.54-123.92, p=0.001) were independent predictors for having urine investigations. CONCLUSION: The highest rate of referral was achieved in males, younger age group, and those who have reached CKD stage 4+5. Urine tests remain largely underutilised and only a minority (16.4%) of patients with an eGFR <30mL/min/1.73m(2) were referred to a NT.