Open-Label Observational Study of a Topical Formulation of Calcium Spirulan Contained in a Defined Extract of the Microalga Spirulina platensis in the Treatment of Children with Molluscum Contagiosum.

Background: Molluscum contagiosum (MC) is a common viral skin infection primarily affecting children which is difficult to treat using available therapeutic approaches. The sulfated polysaccharide named calcium spirulan (Ca-SP) has demonstrated antiviral effects against herpes simplex virus in keratinocytes in vitro, and a cream containing 1.5% Ca-SP and 1% of a defined microalgae extract (Spiralin®) effectively prevented herpes labialis in a trial with susceptible individuals. This observational study aimed to show antiviral effects of a similar formulation (Spirularin® VS) against MC in children. Methods: Children with active MC lesions were treated with Spirularin® VS cream twice daily on affected skin over several months and asked to return for follow-up visits after 1 to 3 months. Clinical status of MC infection was documented at baseline and follow-up visits. Results: Of the 31 children enrolled in the study, 26 completed treatment and returned for control visits. Spirularin® VS cream was applied twice daily over a period of 1 to 9 months (mean treatment duration 3.9 months). 19/26 (73.1%) children achieved complete clearance of MC lesions with no clinical evidence of bacterial skin infection during treatment. No irritative skin reactions or unpleasant symptoms were observed or reported. Conclusion: This open-label observational study suggests that a cream formulation containing 1.5% Ca-SP and 1% Spiralin® may be an effective and safe treatment option for children with active MC lesions. The high rate of complete clearance of MC lesions and lack of adverse reactions warrant further investigation in larger, controlled trials.

Basal cell carcinomas of the scalp after radiotherapy for tinea capitis: Clinicopathological study in a case series of 96 patients with analysis of 427 tumours.

BACKGROUND/OBJECTIVES: Low-dose X-ray radiotherapy to treat tinea capitis during childhood is a well-known risk factor for scalp basal cell carcinomas (BCCs). Post-radiotherapy BCCs are often multiple, and it has been suggested that they display more aggressive features. Our main objective was to study the clinicopathological aspects of post-radiotherapy BCCs to evaluate their biological behaviour and identify features that may differ from other BCCs. METHODS: We performed an observational, retrospective study assessing multiple clinical and pathological characteristics of patients with post-radiotherapy BCCs. RESULTS: We studied 96 patients with 427 post-radiotherapy scalp BCCs. Post-radiotherapy BCCs were often multiple (median of 4 lesions/patient, ranging from 1 to 54). Significant comorbidities included a high incidence of thyroid disease and meningiomas. Recurrences were observed in 23% of patients, but there may be confounding factors, such as referral bias, heterogenous treatment modalities and occurrence of new tumours due to field effect. We found a high incidence of infundibulocystic BCCs (in 14.6% of patients and corresponding to 5.4% of the total number of tumours), trichoblastomas (5.2%) and neurofibromas of the scalp (10%). CONCLUSIONS: This study is consistent with the occurrence of multiple lesions (sometimes numerous) and a relatively high tendency for recurrence in post-radiotherapy BCCs, as suggested by previous studies. We also found a high incidence of the infundibulocystic variant and a higher risk of follicular tumours and neurofibromas, which suggests that radiotherapy may influence the type of differentiation of BCCs and contribute to induce neoplasms of different cell lines.

Basal Cell Carcinomas After Radiotherapy Show More Frequent Follicular Differentiation Than Tumors From Sun-Exposed Areas: Immunohistochemical Study With a Special Focus on Infundibulocystic Basal Cell Carcinoma.

ABSTRACT: Patients submitted to radiotherapy for tinea capitis in childhood have an increased incidence of scalp basal cell carcinomas (BCCs) but also of other neoplasms, namely, follicular tumors. In a cohort of such patients, we also found a high incidence of infundibulocystic BCCs, an otherwise rare variant. We thus hypothesized that postradiotherapy BCCs could be more prone to display follicular differentiation. We compared the histological and immunohistochemical features of postradiotherapy BCCs [both conventional (16 cases) and infundibulocystic (16 cases)] with those of BCCs arising in sun-exposed areas (16 cases), using markers of follicular differentiation (PHLDA-1, CK15, CD34, ß-catenin, and calretinin). Postradiotherapy BCCs showed slightly higher tendency for infundibular and/or trichilemmal differentiation than BCCs from sun-exposed areas (37.5% vs. 18.8%), but this difference was not statistically significant. Nevertheless, infundibulocystic BCCs showed more frequent expression of PHLDA-1 and stronger cytoplasmic expression of CK15 compared with the other lesions. In addition, CD34 highlighted a characteristic meshwork of stromal cells surrounding the epithelial component in all infundibulocystic BCCs, in contrast to the other postradiotherapy BCCs and UV-related BCCs, in which 78.1% were negative or only focally positive. In conclusion, our study suggests a tendency for more frequent follicular differentiation in postradiotherapy BCCs compared with BCCs from sun-exposed areas. In addition, the immunohistochemical study confirms previous data from the literature regarding infundibulocystic BCCs (higher CK15 and PHLDA-1 expression) and shows a distinctive stromal positivity for CD34 that has not been previously acknowledged in these tumors.

Histopathology of chronic spontaneous urticaria with occasional bruising lesions is not significantly different from urticaria with typical wheals.

BACKGROUND: Chronic spontaneous urticaria (CSU) may occasionally exhibit long-lasting lesions with bruising, usually considered a hallmark of urticarial vasculitis (UV). Histopathology of these chronic urticarial lesions has not been extensively studied. METHODS: Skin biopsies from patients with anti-H1 resistant CSU were evaluated for several parameters (edema, location, intensity, and cell composition of the inflammatory infiltrate, and abnormalities in the blood vessels). RESULTS: We studied 45 patients (37 female/8 male, mean age 49.3 years) with CSU, 60% of whom with occasional bruising lesions and 3 patients with hypocomplementemic UV. Histopathology in CSU showed mainly perivascular and interstitial inflammatory infiltrate (91.1%), including eosinophils (80%), neutrophils (77.8%), and lymphocytes (71.1%), vasodilatation (88.9%), intravascular neutrophils (95.6%), dermal edema (51.1%), swelling of endothelial cells (51.1%), and minor and rare fibrinoid necrosis and karyorrhexis (6.7%). Significant karyorrhexis and frank fibrinoid necrosis were observed, respectively, in two and three cases of UV. In patients with occasional bruising, mast cells occurred in fewer cases whereas eosinophils were more frequent, but no statistically significant difference was found for other parameters. CONCLUSIONS: Histopathological findings were not significantly different between CSU with or without bruising lesions. Bruising may be associated with more severe forms of CSU with no histopathological signature, although UV cannot be completely excluded based on histopathology.

Multiple Basal Cell Carcinomas of the Scalp After Radiotherapy: Genomic Study in a Case With Latency Period Over 80 Years.

ABSTRACT: Basal cell carcinoma (BCC) has been linked mostly to ultraviolet radiation exposure, but ionizing radiation has also been implicated in the genesis of a subset of BCCs occurring after radiotherapy. We present a 93-year-old woman with 4 BCCs of the scalp after radiotherapy for tinea capitis, diagnosed after a latency period of over 80 years. The largest lesion was located on the right temporal region and corresponded to a BCC of mixed type, with nodular, infiltrative, and micronodular components. We performed genomic study with array comparative genomic hybridization in samples from each BCC, which revealed more imbalances in the largest lesion than in the remaining ones, correlating with its higher histological complexity. Furthermore, this was the only lesion presenting loss at 2p22.3, where is mapped the BIRC6 gene associated with regulation of apoptosis, and loss at 16q24.3, where is mapped FANCA gene, responsible for DNA repair and maintenance of chromosome stability. Despite these differences, there were aberrations shared by all tumor samples, suggesting a common genetic signature. Our report describes, to the best of our knowledge, the longest latency period between exposure to radiotherapy and the diagnosis of BCC. The genomic study showed imbalances common to all tumor samples but also differences that could explain their heterogeneity in terms of histological subtype and biological potential. In addition, these differences could also be a consequence of different times in the evolution of the lesions at the moment of presentation, thus having a diverse combination of accumulated genomic imbalances.

Specific cutaneous infiltrates in patients with haematological neoplasms: a retrospective study with 49 patients.

BACKGROUND: Haematological neoplasms account for around 9% of all cancers, and they are recognised as an important cause of skin infiltration. However, studies analysing cutaneous metastasis of haematological neoplasms are scarce. We describe the clinical spectrum and outcomes of specific cutaneous manifestations of leukaemias, lymphomas, multiple myeloma (MM), and blastic plasmacytoid dendritic cell neoplasm (BPDN) and make a review of the literature. METHODS: Data from 49 patients diagnosed with secondary cutaneous infiltration of systemic haematological neoplasms over the last 10 years in a tertiary dermatology centre were retrospectively collected, and clinical-evolutive features were analysed. RESULTS: Most cases were lymphoma (44.9%, n = 22), followed by leukaemia cutis (38.8%, n = 19), secondary plasmacytoma (10.2%, n = 5) and BPDN (6.1%, n = 3). Nodules were the predominant type of lesion, and most patients presented with multiple (≥3) lesions. In 51% (n = 25) of cases, cutaneous infiltration was detected before the diagnosis of the underlying malignancy. The patients in diverse nosological groups did not differ in terms of survival (P = 0.052). CONCLUSIONS: We recognise the clinical heterogeneity of specific cutaneous infiltrates. The high proportion of cases in which skin involvement was key to the diagnosis of systemic malignancy emphasises the role of the dermatologist in recognising and correctly managing these patients.

Basal cell carcinomas of the scalp after radiotherapy for tinea capitis in childhood: A genetic and epigenetic study with comparison with basal cell carcinomas evolving in chronically sun-exposed areas.

BACKGROUND: Basal cell carcinoma (BCC) has been mostly associated with sun exposure, but ionizing radiation is also a known risk factor. It is not clear if the pathogenesis of BCC, namely at a genomic and epigenetic level, differs according to the underlying triggering factors. OBJECTIVE: The present study aims to compare genetic and epigenetic changes in BCCs related to ionizing radiation and chronic sun exposure. METHODS: Tumor samples from BCCs of the scalp in patients submitted to radiotherapy to treat tinea capitis in childhood and BCCs from sun-exposed areas were analysed through array comparative genomic hybridization (array-CGH) and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) to detect copy number alterations and methylation status of specific genes. RESULTS: Genomic characterization of tumor samples revealed several copy number gains and losses in all chromosomes, with the most frequent gains observed at 2p, 6p, 12p, 14q, 15q, 18q, Xp and Yp, and the most frequent losses observed at 3q, 14q, 16p, 17q, 22q, Xp, Yp and Yq. We developed a statistical model, encompassing gains in 3p and 16p and losses in 14q and 20p, with potential to discriminate BCC samples with sporadic aetiology from BCC samples that evolve after radiotherapy in childhood for the treatment of tinea capitis, which presented statistical significance (P = 0.003). Few methylated genes were detected through MS-MLPA, most frequently RARB and CD44. CONCLUSIONS: Our study represents a step forward in the understanding of the genetic mechanisms underlying the pathogenesis of BCC and suggests potential differences according to the underlying ris k factors.

Toxic epidermal necrolysis-like subacute cutaneous lupus erythematosus associated with lung carcinoma.

Specific vesiculobullous skin lesions in lupus erythematosus (LE) are rare and must be differentiated from toxic epidermal necrolysis (TEN), TEN-like dermatoses and other vesiculobullous conditions. We report a patient with typical subacute cutaneous lupus erythematous that progressed with large sheet-like areas of epidermal detachment and Nikolsky sign resembling TEN. She had a serological profile suggestive of underlying connective tissue disease, histological findings of interface dermatitis with a lymphocytic infiltrate, positive direct immunofluorescence, resolution with immunomodulation and lack of a culprit drug, features observed in TEN-like cutaneous lupus erythematous. Furthermore, she was diagnosed with lung carcinoma, an association that has been previously reported. Differentiating a bullous eruption in the context of pre-existing LE remains difficult requiring a thorough analysis of clinical and histopathological data.

Erythema nodosum and sarcoid granulomas - letting the cat out of the bag.

A 41-year-old woman presented with a violaceous papule on the dorsum of the hand, large ipsilateral axillary lymphadenopathy, and tender, erythematous, subcutaneous nodules on the legs. Accompanying signs included fever, ankle swelling, and bilateral red eye. She recalled having a previous exposure to kittens one month before and had a positive family history for sarcoidosis. Histological examination of the hand lesion showed sarcoidal granulomas with positive Bartonella henselae DNA, whereas a biopsy done on the leg nodules was compatible with erythema nodosum. Cat scratch disease (CSD) typically presents as a tender regional lymphadenopathy preceded by an inoculation papule with spontaneous resolution occurring between 8-16 weeks. Cutaneous manifestations of CSD are rare, with erythema nodosum accompanying only 0.6% of cases. Although speculative, the background of a positive family history for sarcoidosis may explain the atypical presentation of this case, with red eye, persistent arthralgia, and associated sarcoidal granulomas.

Histological variability and the importance of clinicopathological correlation in cutaneous Rosai-Dorfman disease.

Rosai-Dorfman disease is a benign histiocytic proliferative disorder of unknown etiology. The disease mainly affects lymph node tissue, although it is rarely confined to the skin. Here, we describe a 53-year-old woman with purely cutaneous Rosai-Dorfman disease. The patient presented with a large pigmented plaque on her left leg, and sparse erythematous papules on her face and arms. A complete clinical response was achieved with thalidomide, followed by recurrence at the initial site one year later. The histological examination displayed the typical features of Rosai-Dorfman disease in the recent lesions but not in the older lesions. In the setting of no lymphadenopathy, the histopathological features of Rosai-Dorfman disease are commonly misinterpreted. Therefore, awareness of the histological aspects present at different stages, not always featuring the hallmark microscopic signs of Rosai-Dorfman disease, is particularly important for a correct diagnosis of this rare disorder.

Histological variability and the importance of clinicopathological correlation in cutaneous Rosai-Dorfman disease

Abstract: Rosai-Dorfman disease is a benign histiocytic proliferative disorder of unknown etiology. The disease mainly affects lymph node tissue, although it is rarely confined to the skin. Here, we describe a 53-year-old woman with purely cutaneous Rosai-Dorfman disease. The patient presented with a large pigmented plaque on her left leg, and sparse erythematous papules on her face and arms. A complete clinical response was achieved with thalidomide, followed by recurrence at the initial site one year later. The histological examination displayed the typical features of Rosai-Dorfman disease in the recent lesions but not in the older lesions. In the setting of no lymphadenopathy, the histopathological features of Rosai-Dorfman disease are commonly misinterpreted. Therefore, awareness of the histological aspects present at different stages, not always featuring the hallmark microscopic signs of Rosai-Dorfman disease, is particularly important for a correct diagnosis of this rare disorder.

Vancomycin-induced linear IgA bullous dermatosis: associations.

UNLABELLED: Linear IgA bullous dermatosis (LABD) is a rare autoimmune blistering disease. LABD is considered mostly idiopathic, butsome cases have been reported to be drug-induced, mainly associated with vancomycin (VCM).We present two cases of LABD possibly associated with VCM used for cardiac surgery prophylaxis; in the presented cases, the eruptions occurred only after VCM withdrawal, therefore leaving a question about the relationship between VCM and LABD in these cases.We reviewed previous reports of VCM-induced LABD and analyzed the following parameters: gender, age, recent medical history, concurrent medication, latency period, progression after withdrawal, time to resolution, treatment, and rechallenge. RESULTS: The causal relationship between VCM and LABD was often unclear; patients frequently had concurrent medication and symptoms frequently began and/or progressed after VCM withdrawal. Among the 46 reviewed patients in addition to our two cases (n=48), 20 (42%) had recent history of cardiac procedure, cardiac infection, congestive heart failure, or aortic aneurism. CONCLUSION: Further investigation is needed to ascertain the association between LABD, VCM, and heart disease.

Superficial Epidermolytic Ichthyosis-Hypertrichosis as a Clue to Diagnosis.

Superficial epidermolytic ichthyosis (SEI) is an autosomal dominant disorder caused by a mutation in the keratin 2 gene and clinically characterized by mild hyperkeratosis, superficial blisters and shedding, referred to as the moulting phenomenon. We report a case of SEI in an 18-month-old girl presenting with marked hypertrichosis. Although not invariably present, we believe that hypertrichosis can be an important clue for diagnosis.