Neuroendocrine Transdifferentiation in Cutaneous Melanoma: A Case Report and Review of the Literature.

ABSTRACT: Neuroendocrine transdifferentiation refers to the progressive transformation of a nonneuroendocrine tumor to the one showing evidence of neuroendocrine differentiation on morphological and immunohistochemical grounds. Although this phenomenon has been well-documented in certain malignancies, particularly prostatic adenocarcinoma after androgen deprivation, cases of neuroendocrine transdifferentiation in melanomas are exceptionally rare. Herein, we report a case of a conventional superficial spreading melanoma occurring on the skin of the leg in a young male which showed progressive neuroendocrine transdifferentiation as it progressed through 2 in-transit metastases and a nodal metastatic deposit over a 4-year period. The tumor retained the BRAF V600E mutation throughout the disease process, and disease control was achieved through dual BRAF inhibition therapy. The possibility of melanoma masquerading as a high-grade neuroendocrine malignancy when investigating tumors of unknown primary should be kept in the mind of clinicians and histopathologist alike as a potential diagnostic pitfall, thus helping avoid misdiagnosis and guide appropriate treatment strategies.

Neutrophilic dermatosis of the dorsal hands: A review of 123 cases.

Neutrophilic dermatosis of the dorsal hands (NDDH) is an uncommon localized variant of Sweet syndrome first described in 1995. It is characterized by tender erythematous plaques, pustules, and bullae on the dorsa of the hands. A total of 123 cases of NDDH are included in this review. The mean patient age was 62.1 years, and there was a slight female preponderance. Overall, 78.0% of cases had bilateral involvement, and other sites were affected in almost a third of cases. Underlying disease was found in ∼40% of patients, with the most common associations being hematologic disorders (gammopathies, myelodysplasias, or malignancies), recent infection, solid organ tumors, and inflammatory bowel disease. Systemic or topical corticosteroids or both were employed in the treatment of 88.1% of cases, while dapsone, colchicine, and tetracyclines were the most common steroid-sparing agents used. Improvement was often rapid and complete resolution the norm. Although uncommon, NDDH is frequently misdiagnosed, and thus, its exact prevalence is probably underestimated. Misdiagnosis might have significant implications, including treatment delays or incorrect management. Moreover, recognition of NDDH is important, since a correct diagnosis should trigger a search for underlying diseases and proper treatment with corticosteroids, steroid-sparing agents, or both, which is almost invariably curative.

Retiform Purpura of the Lower Limbs Associated with Levamisole-Adulterated Cocaine.

A young man was treated in hospital for sepsis, disseminated intravascular coagulation and multi-organ failure. He was a regular intranasal cocaine user up to 1 day prior to symptom onset. Clinical examination revealed extensive retiform purpura affecting both his lower limbs. Skin biopsy revealed widespread thrombosis in the small- and medium-sized vessels of the mid dermis and the subcutaneous fat with surrounding leucocytoclasis. There was also extensive ischaemic necrosis of the upper reticular and papillary dermis and focal ischaemic necrosis of the epidermis. These findings were in keeping with a thrombotic vasculopathy with associated cutaneous ischaemic necrosis, likely associated with levamisole-adulterated cocaine (LAC). An autoimmune screen showed extremely raised levels of anti-B2-glycoprotein IgM, IgG and anti-cardiolipin IgG antibodies, usually seen in antiphospholipid syndrome (APS). The literature describes how APS could be secondary to various underlying conditions, including LAC, and that levamisole toxicity may mimic APS and hence be missed. LEARNING POINTS: Levamisole is a common adulterant found in cocaine; the resultant toxicity can present with cutaneous manifestations, namely retiform purpura and skin necrosis, similar to antiphospholipid syndrome.Patients presenting with such features should be asked about illicit drug use, specifically cocaine, and investigated by screening urine for drugs of abuse and serum antihuman elastase antibody when possible.

The international EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria.

This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA²LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous or inducible urticaria is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.

Plasma Total Ascorbic Acid and Serum 25-Hydroxy-Vitamin-D Status in Patients with Venous Leg Ulcers: A Case-Control Study.

Venous leg ulcers (VLUs) pose a significant burden on patients, health care systems, and national economies. Nutritional health is an important determinant of wound healing. Vitamin C and D levels and additional biochemical markers, C-reactive protein, and albumin in a group of patients with VLUs, were compared with a control group without VLUs. No significant difference in either nutrient marker was found with the presence, size, or duration of VLUs. Obesity was significantly more common in the VLU group, as noted in other studies. Additional controlled studies should be performed with measures of VLU size and duration to assess long-term outcomes with nutritional therapy.

Variegate Porphyria Triggered by Acute Hepatitis A Infection.

BACKGROUND: Variegate porphyria (VP) is a rare disorder of haem biosynthesis. We report a novel association with hepatitis A infection. PATIENT AND METHODS: A 31-year-old man was diagnosed with acute hepatitis A infection. During recovery, he presented with abdominal pain and a photoaggravated blistering skin eruption. RESULTS: Urine porphyrin precursors were markedly raised with high coproporphyrin III isomer levels. Faecal protoporphyrin levels were markedly increased and a maximum plasma fluorescence emission at 629 nm was noted. DISCUSSION: Acute hepatitis A infection, and the associated metabolic stress exerted on the haem biosynthetic pathway, induced overt presentation of latent VP. LEARNING POINTS: There should be a high index of suspicion for an acute cutaneous porphyria when a photosensitive rash is accompanied by neurovisceral symptoms.Latent porphyria may be overtly manifested after appropriate triggers which stress the metabolic haem biosynthetic pathway. One such trigger demonstrated by this case presentation is acute hepatitis A infection.The diagnostic approach to the investigation of a suspected acute cutaneous porphyria is initially with light-protected samples for urinary porphyrin precursors and plasma for fluorescence scanning. These should be sampled ideally during symptomatic periods. Further specialist analysis with fractionation of urinary and faecal porphyrins is necessary to distinguish between the two different acute cutaneous porphyrias.

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.

Complete Clearance of Resistant Granuloma Faciale With Pulsed Dye Laser After Pre-treatment With Mometasone and Tacrolimus.

Introduction: Granuloma faciale is an uncommon inflammatory dermatosis which usually affects the face and is often resistant to treatment. Case Report: A 39-year-old English lady with Fitzpatrick skin phototype II presented with typical lesions of granuloma faciale, confirmed on biopsy, on her cheeks and nose. Treatment with ScleroPlus pulsed dye laser (Candela Corporation, Wayland, Mass) produced no visible improvement. The patient re-presented 5 years later with the same lesions, now more prominent. No improvement was noted with topical mometasone, however addition of topical tacrolimus caused significant flattening. Since the erythema and telangiectases persisted, treatment with ScleroPlus pulsed dye laser was re-attempted. Treatments were performed with a wavelength of 595 nm, pulse duration of 1.5 ms and 7 mm spot at a fluence of 8.5 J/cm2 in the first session and 9.5 J/cm2 in the subsequent 2 sessions. This resulted in complete resolution without scarring or pigmentary change. There was no recurrence at follow-up one year later. Conclusion: Our observation supports the use of combination therapy in resistant cases of granuloma faciale. One such combination would be the application of a topical corticosteroid and tacrolimus followed by pulsed dye laser.