Dupilumab ocular side effects in patients with atopic dermatitis: a systematic review.

Atopic dermatitis (AD) is a chronic, inflammatory skin disorder that most frequently occurs in children, but it can also affect adults. Even though most AD cases can be managed with topical treatments, moderate-to-severe forms require systemic therapies. Dupilumab is the first human monoclonal antibody approved for the treatment of AD. Its action is through IL-4 receptor alpha subunit inhibition, thus blocking IL-4 and IL-13 signaling pathways. It has been shown to be an effective, well-tolerated therapy for AD, as well as for asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), and eosinophilic esophagitis (EoE). However, an increasing incidence of dupilumab-induced ocular surface disease (DIOSD) has been reported in patients treated with dupilumab, as compared to placebo. The aim of this study was to summarize scientific data regarding DIOSD in AD patients treated with dupilumab. A search of PubMed and clinicaltrials.gov databases was performed. There was no limit to study design. All AD cases were moderate-to-severe. DIOSD was either dermatologist-, allergist-, or ophthalmologist-assessed. Evidence shows that DIOSD occurs most frequently in patients with atopic dermatitis and not in other skin conditions, neither in patients with asthma, CRSwNP, nor EoE who are on dupilumab treatment. Further studies are warranted in order to establish a causal relationship between dupilumab and ocular surface disease. Nevertheless, ophthalmological evaluations prior to dupilumab initiation can benefit AD patients with previous ocular pathology or current ocular symptomatology. Also, patch testing for ocular allergic contact dermatitis might be advantageous in patients with a history of allergic conjunctivitis. Furthermore, TARC, IgE, and circulating eosinophils levels might be important biomarkers for a baseline assessment of future candidates to dupilumab treatment. However, TARC measurements should be resumed for research purposes only.

Minimizing the dermatoscopic morphologic overlap between basal and squamous cell carcinoma: a retrospective analysis of initially misclassified tumours.

BACKGROUND: Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) have well-established dermatoscopic criteria that make them relatively easy to recognize on a clinical basis. However, even with the addition of dermatoscopy, a morphologic overlap between the two tumours does exist. OBJECTIVES: To analyse the dermatoscopic morphology of clinically and dermatoscopically misclassified BCCs and SCCs, to identify factors causing the erroneous clinical interpretation and, therefore, minimize the morphologic overlap between BCC and SCC. METHODS: Retrospective study including histopathologically diagnosed BCCs or SCCs that had been clinically inversely diagnosed. Their dermatoscopic images were blindly evaluated for the presence of predefined criteria. Descriptive statistics were performed and univariate and multivariate predictors were calculated. RESULTS: A total of 68 cases were included, 41 of which were BCCs and 27 SCCs. Most tumours in both groups were non-pigmented, ulcerated and displayed a polymorphous vascular pattern. The presence of erosions was positively associated to BCC (5.2-fold higher odds, P = 0.05), whereas scales/keratin masses were positively associated to SCC (3.7-fold higher odds, P = 0.07), although marginally not statistically significant. CONCLUSIONS: Clinically misclassified BCCs and SCCs are usually non-pigmented ulcerated tumours. Erosions and keratin masses/scales are more robust criteria as compared to vascular structures for the differential diagnosis between BCC and SCC.

Multicenter clinical trial on the performance and tolerability of the Hyaluronic acid-collagenase ointment for the treatment of chronic venous ulcers: a preliminary pilot study.

BACKGROUND: Bed debridement is important to treat chronic wounds. Effective agents should remove the necrosis but protect the granulation tissue. We evaluated the performance and tolerability of a new composite ointment containing collagenase and hyaluronic acid for chronic venous ulcers. PATIENTS AND METHODS: Subjects with class 6 venous ulcers (CEAP classification) of at least 6 months duration were prospectively recruited. The ointment was administered daily and follow-up visits were conducted on the fifth, 10th, 15th and 20th days. On each visit the necrotic area was measured with a grid. The moisture balance, odour, viability of non-necrotic areas and the presence of erythema were also assessed. Primary outcome was the percentage of subjects with complete debridement, secondary outcomes the time to complete healing, reduction of the lesion area, absence of necrotic tissue, presence of odor, erythema, hydration, any adverse events. RESULTS: One hundred subjects were enrolled in four centres. All patients achieved complete debridement of the necrotic area and a significant reduction of the total ulcer area by day 20, while other parameters improved significantly over time. Only two patients experienced a transient leg oedema. CONCLUSIONS: The combination of collagenase and hyaluronic acid is safe and effective for chronic venous ulcers.

Secondary involvement of lymph nodes in Kaposi sarcoma.

Kaposi sarcoma is a low-grade neoplasm first described by Moricz Kaposi in 1872. Although many attempts have been made to explain its pathogenesis, its etiology still remains obscure. In this regard, many aspects of the disease's genetic, epidemiological and histopathological backgrounds are even today unclear. We present the case of a 57-year-old male patient, constant HIV negative, with a history of plaque-like lesions on his right foot approximately two years ago. Following surgical removal, a diagnosis of Kaposi sarcoma, plaque stage was settled. One year after, the patient was admitted to the hospital for pain in the right ankle and foot, associated to paresthesis and trophic lesions at this level. Similar lesions developed in the popliteal fossa. Biopsy and subsequent histological and immunohistochemical examination revealed a KS at that level. The most recent hospital admission revealed the appearance of an indolent lymphadenopathy in the groin. Our case represents a rare occurrence of Kaposi sarcoma at a HIV-negative patient, which, after several local recurrences and progressive behavior, produced a lymph node involvement at the groin level. The immunohistochemical assessments have confirmed the diagnosis.

Cardiac allograft vasculopathy in adult human recipients: a case series of seven patients and review of literature.

BACKGROUND: Chronic rejection (CR) also called cardiac allograft vasculopathy (CAV) is, besides infections and malignant tumors, the leading cause of death during the late period of post-heart transplant. PATIENTS AND METHODS: In this paper, we present a series of seven cases with chronic post-transplant cardiac rejection in the light of our experience related to histopathological aspects, difficulties in diagnosing and survival time. RESULTS: Our study comprises patients whose ages ranked at the time of transplant between 33 and 58 years, with a mean age of 47.71 years, the ratio between men and women being 6:1. Chronic rejection - cardiac allograft vasculopathy occurred in all seven patients comprised in this study, the earliest in the second year post-transplant (three patients), followed by the third year (one patient), the seventh and eighth year (one patient) and the latest survival period being over 11 years (one patient). Four out of the seven patients with chronic rejection events were preceded by episodes of acute cellular rejection. The most convincing indirect evidence of chronic rejection in endomyocardial biopsies were: ischemic events of the myocardiocytes and impaired microvascular network because of perivascular and interstitial fibrosis. CONCLUSIONS: Our study shows that the most important morphological factors correlated with the manifestation of chronic rejection were the episodes of acute cellular rejection or perivascular and interstitial fibrosis, these injuries also being indirect signs mainly detectable at the level of endomyocardial biopsies.