Febrile Ulceronecrotic Mucha-Habermann Disease Associated With Hemophagocytic Lymphohistiocytosis: A Case Report and Review of the Literature.

ABSTRACT: Mucha-Habermann disease (MHD) is an inflammatory skin disease characterized by polymorphous eruptions of erythematous, necrotic macules that have been reported for similarities to cutaneous T-cell lymphoma. Febrile ulceronecrotic MHD (FUMHD) represents a severe variant of MHD, marked by ulcers, hemorrhagic bullae, and systemic symptoms. Herein, we report a case of a severely atypical lymphomatoid expression of FUMHD associated with hemophagocytic lymphohistiocytosis (HLH). A previously healthy 21-year-old woman was admitted to the hospital with a rapidly progressive necrotic papular rash. Physical examination revealed right orbital swelling, bilateral hemorrhagic auricular bullae, and multiple ulcerative purpuric papulonodules on the trunk, face, and extremities. Biopsy indicated a dermal and subcutaneous infiltrate of atypical CD8 + lymphocytes with loss of CD5 and reduction in CD7 expression, along with features of lymphomatoid vasculitis. A diagnosis of a severely atypical lymphomatoid expression of FUMHD was made. The patient also met 7 of 9 HLH-2004 criteria, leading to a diagnosis of HLH. Positron emission tomography/computed tomography, flow cytometry, and rheumatologic workup were unremarkable. Treatment with an eight-week course of etoposide and dexamethasone for HLH led to rapid clinical improvement. Over time, her skin lesions regressed and eventually scabbed over to leave hyperpigmented scars, confirming the diagnosis of MHD. She has remained stable, off therapy for 4 years. Although potentially fatal, FUMHD often exhibits favorable outcomes and may resolve without recurrence, as in our patient. FUMHD should be considered in the differential diagnosis for patients presenting with cutaneous CD8 + necrotizing angiocentric lymphoproliferative disease complicated by HLH.

[Marjolin's ulcer associated with verrucous carcinoma in an immunocompromised patient]. / Úlcera de Marjolin asociada a carcinoma verrugoso en paciente inmunocomprometido.

Background: Marjolin's ulcer is the malignant degeneration of any chronic wound, with a latency period from tissue injury to variable malignant transformation that may occur up to 30 years later. Among the associated neoplasms, squamous cell carcinoma (SCC) is the predominant lineage in up to 71% of cases. The verrucous carcinoma variant has been estimated to have a low presentation, being described in the literature as 2% of all SCC and reported anecdotally in immunosuppressed patients, which justifies the objective of this publication. Clinical case: 65-year-old female patient with a history of being a carrier of human immunodeficiency virus (HIV) infection, who presented a verrucous carcinoma associated to a Marjolin ulcer secondary to herpes zoster and infection of soft tissues in the right leg, with a latency period of 10 years from the initial infectious process to histopathological confirmation. Conclusions: The finding of a verrucous carcinoma on a Marjolin ulcer has been little described in literature, with a lower incidence in the context of a patient with a history of being a carrier of HIV infection, finding 7 case reports, the oldest from 1998. For this reason, it is important to have diagnostic suspicion, to carry out an adequate study protocol and always making clinical-pathological correlation, in order to establish timely and individualized treatment.

Introducción: la úlcera de Marjolin es la degeneración maligna de cualquier herida crónica, con un periodo de latencia desde la lesión tisular a la transformación maligna variable que puede presentarse hasta 30 años después. De las neoplasias asociadas, el carcinoma espinocelular es la estirpe predominante hasta en 71% de los casos. La variante de carcinoma verrugoso se ha estimado con una presentación baja, pues ha sido descrito en la literatura como el 2% de todos los carcinomas espinocelulares y reportado de manera anecdótica en pacientes inmunosuprimidos, lo que justifica el objetivo de esta publicación. Caso clínico: mujer de 65 años con el antecedente de ser portadora de infección por virus de inmunodeficiencia humana (VIH), que presentó un carcinoma verrugoso asociado a una úlcera de Marjolin secundaria a herpes zóster e infección de tejidos blandos en pierna derecha, con un periodo de latencia de 10 años desde el proceso infeccioso inicial hasta la confirmación histopatológica. Conclusiones: el hallazgo de un carcinoma verrugoso asentado sobre una úlcera de Marjolin ha sido poco descrito en la literatura, con una menor incidencia en el contexto de un paciente con antecedente de ser portador de infección por VIH, ante lo cual encontramos 7 reportes de caso, el más antiguo de 1998. Por este motivo es importante contar con la sospecha diagnóstica, para poder hacer un protocolo de estudio adecuado y siempre haciendo correlación clínico-patológica, con la finalidad de instaurar un tratamiento oportuno e individualizado.

"Hurricane-like" Presentation of a Recurrent Marjolin's Ulcer in a Young Female.

Marjolin's ulcer (MU) with rapid progression and multiple distant metastases is rare. We report a case of an MU of the thigh developing in a postburn scar, which after successful R0 resection developed multiple bony and visceral metastasis to femur, vertebra, skull, lung, and liver within 3 months of excision. We highlight the "hurricane-like" recurrence in an MU, which is unusual for the metachronous disease. We stress that MUs, unlike conventional wisdom, need a thorough metastatic workup at presentation, and prognostication of a possible rapidly progressive course after surgery which may lead to grave prognosis and mortality.

Diagnosis and management of systemic sclerosis-related calcinosis.

INTRODUCTION: Calcinosis is common in patients with systemic sclerosis (SSc) and refers to the sub-epidermal deposition of calcium salts in the skin. SSc-related calcinosis is associated with significant morbidity, including through cutaneous ulceration and predisposition to become infected. AREAS COVERED: After briefly addressing aetiopathogenesis, we describe the clinical burden of SSc-associated calcinosis and provide a structured and practical clinical approach to diagnosis and assessment, including discussion of the role of different imaging modalities. The multi-faceted treatment of SSc-associated calcinosis is presented under three broad headings of 'general measures,' and 'medical treatment' and 'surgical treatment.' We adopted a narrative approach to identify relevant manuscripts to inform our review. EXPERT OPINION: SSc-related calcinosis is an area of major unmet clinical need and for too long has been a neglected area of research. Safe and effective treatments are badly needed to improve patient quality of life and outcomes. To facilitate future clinical trials, we require increased understanding of pathogenesis (to inform selection of potential targeted therapies) and reliable outcome measures, including those which will measure the impact and severity of calcinosis from the patient perspective. International collaborative research is ongoing to develop outcome measures and treatments for this potentially devastating complication of SSc.

The Effects of Skin Temperature Changes on the Integrity of Skin Tissue: A Systematic Review.

OBJECTIVE: To determine whether changes in skin temperature can affect the integrity of skin. METHODOLOGY: The authors conducted a systematic literature search as per the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. They searched the CINAHL (Cumulative Index to Nursing and Allied Health Literature), Cochrane, MEDLINE Complete, Academic Search Ultimate, and HyDi databases for articles examining the effects of skin temperature on skin integrity published through April 2020. Two independent reviewers scored the methodologic quality of the 13 included studies. RESULTS: Only 11 studies were included in the qualitative analysis, as the other two articles had a critical risk of bias. There is strong evidence to indicate that an increase in skin temperature leads to changes in skin structure and function. However, ulcer formation was more affected by intrinsic and extrinsic factors, rather than by temperature alone. CONCLUSION: Further high-quality randomized controlled trials are required to investigate the direct effect of skin temperature on ulceration.

Neuropathic ulcers in leprosy: clinical features, diagnosis and treatment.

Leprosy is a neglected disease caused by Mycobacterium leprae and Mycobacterium lepromatosis, and is related to significant disabilities resulting from the neural damage generated by this mycobacteria. Neuropathic ulcers-lesions that can appear at the plantar and extra-plantar levels-are one such disability, and diagnosis requires an adequate dermatological, neurological and microbiological evaluation. The treatment of these lesions is based on a multidisciplinary approach that includes debridement of the necrotic tissue, controlling infections, reducing pressure areas, optimising blood flow, and nerve decompression. This review aims to describe the clinical features, diagnostic methods and treatment of neuropathic ulcers in leprosy. The diagnostic methods and medical management used in leprosy ulcers are based on those used for diabetic foot. This requires radical change as these diseases are immunologically and physiologically very different.

A rare case of lues maligna in an HIV-negative woman.

We describe an HIV-negative 43-year-old woman presenting with a diffuse ulceronodular eruption and positive serological tests for syphilis consistent with lues maligna. Lues maligna is a severe and rare variant of secondary syphilis characterized by prodromal constitutional symptoms followed by the formation of multiple well-circumscribed nodules with ulceration and crust. This case depicts a particularly rare presentation as lues maligna usually involves HIV-positive men. The clinical presentation of lues maligna can pose a diagnostic challenge, with infections, sarcoidosis, and cutaneous lymphoma as just a few entities in its broad differential diagnosis. However, with a high index of suspicion, clinicians can diagnose and treat this entity earlier and reduce morbidity.

Post-burn scar malignancy: 5-year management review and experience.

The study spotlights a severe uncommon post-burn complication, Marjolin's ulcer, in upper Egypt plastic and wound care centres. This problem is mainly related to inadequate medical care and awareness. No community or race is immune. The underlying malignant transformation mechanism remains unclear. The study aims, according to our experience, to review the prognostic factors through the management protocol of Marjolin's ulcers. This prospective study was conducted in the Aswan University Plastic & Burn surgery department in South Egypt between 2013 and 2020 and investigated 226 patients with chronic post-burn ulceration. Nineteen cases were proved to have Marjolin's ulcer, and the other cases that had been excluded from being malignant went for reconstruction with split-thickness skin graft with/without flap after adequate ulcer debridement. The surgical, oncologic, radiologic indications, and prognostic factors were reviewed according to our management outcome-the assessment with follow-up period extended over 5 years. Histopathology of ulcers ranged among mild, moderate, and poorly differentiated squamous cell carcinoma. One scalp ulcer case showed basosquamous pathology. Most cases presented at age above 50, but no age was immune. The mean latent period was 29 years on average. The lesions' sites varied in their anatomic location where they involved the upper extremity, the scalp, and the lower extremity that had a predilection. Although surgical excision is the primary management line for tumour ablation, other factors may change the management course. During the follow-up period, neoplasm recurrence in the form of lymph node enlargement and/or locoregional metastasis was detected in eight cases. Within 1 year after the intervention, six recurrent cases died, and two were saved. In addition to the case study, this paper reviewed the literature and provided our team a good experience in light of the NCCN protocol for non-melanotic cutaneous carcinoma, although we suffered limited medical resources. It is concluded that early accurate diagnosis, low-grade malignancy, and well-planned individualised surgery with adjuvant radiotherapy were the best prognostic factors. The close follow-up for an early sign of disease recurrence is paramount.

[Marjolin ulcers after cultured epidermal autograft in severely burned patients: a rare case series and literature review]. / Marjolin ulcers after cultured epidermal autograft in severely burned patients: a rare case series and literature review.

The advent of tissue engineering and the clinical applications with cultured epidermal autograft (CEA) have improved the prognosis of severely burned patients. Marjolin ulcers (MUs) are a well-known complication of burns. These malignant neoplasm transformations of burn scars are usually squamous cell carcinomas with a higher incidence of regional metastases. Radical surgery remains the treatment of choice. To identify cases of malignant transformation occurring at sites of CEA in a cohort of 68 massively burned patients. A retrospective single-centre study was performed from April 2017 to June 2019 at the Military Hospital of Clamart (France). A total of 34 patients treated between 1991 and 2013 (including one post-mortem) were included. Four cases of squamous cell carcinoma occurred in areas previously covered by CEA. The data from clinical and histopathological examination as well as treatment modalities are presented. One patient died as a result of the evolution of his squamous cell carcinoma, and two others required salvage amputation due to locoregional recurrence. The prevalence of these CEA-MUs is estimated at between 5.9% and 11.7% and the person-time incidence rate of CEA-related MUs is about 5.9 per 1,000 persons-years. In our study, the average time to malignant transformation seems considerably shortened (32-35 years for "classic burn MU" versus 15.7 years for CEA-MU). This first documented case series of CEA-MUs demonstrates the need to inform caregivers and educate patients. Further studies are needed to specify the true incidence of CEA-graft site malignancy.

Calcification in Werner syndrome associated with lymphatic vessels aging.

In addition to the symptoms of aging, the main symptoms in Werner syndrome (WS), a hereditary premature aging disease, include calcification of subcutaneous tissue with solid pain and refractory skin ulcers. However, the mechanism of calcification in WS remains unclear. In this study, the histological analysis of the skin around the ulcer with calcification revealed an accumulation of calcium phosphate in the lymphatic vessels. Moreover, the morphological comparison with the lymphatic vessels in PAD patients with chronic skin ulcers demonstrated the ongoing lymphatic remodeling in WS patients because of the narrow luminal cross-sectional area (LA) of the lymphatic vessels but the increment of lymphatic microvessels density (MLVD). Additionally, fluorescence immunohistochemical analysis presented the cytoplasmic distribution and the accumulation of WRN proteins in endothelial cells on remodeling lymphatic vessels. In summary, these results point out a relationship between calcification in lymphatic vessels and the remodeling of lymphatic vessels and suggest the significance of the accumulation of WRN mutant proteins as an age-related change in WS patients. Thus, cytoplasmic accumulation of WRN protein can be an indicator of the decreasing drainage function of the lymphatic vessels and the increased risk of skin ulcers and calcification in the lymphatic vessels.

Loss of miR-1469 expression mediates melanoma cell migration and invasion.

Tumor ulceration is considered one of the most prognostically significant findings in primary cutaneous melanoma, associated with decreased disease-free and overall survival. However, the unique features associated with ulcerated melanoma that contribute to a poor prognosis in affected patients remain poorly defined. microRNAs are small, non-coding RNAs that function to inhibit expression of specific gene targets, therefore altering the functions of cells in which they are expressed. miR-1469 is a novel miR with significantly decreased expression in ulcerated melanoma tissue relative to non-ulcerated tumors. We hypothesized that loss of miR-1469 expression in melanoma contributes to altered tumor cell functions mediating disease progression. Transfection of a miR-1469 mimic resulted in a significant reduction in the migratory and invasive capacity of the CHL1 and MEL39 melanoma cell lines (>58.1% reduction, p < 0.0332), as well as the invasive capacity of the A375 melanoma cell line (>50% reduction, p < 0.0021). Expression of myeloid cell leukemia-1 (MCL1), a miR-1469 target gene, was reduced in the A375 and MEL39 cell lines by immunoblot. No significant differences in viability, resistance to apoptotic stimuli, or proliferation were observed following transfection. These findings together demonstrate how migration and invasion are specific functions through which miR-1469 expression in melanoma cells can contribute to the differences in disease progression associated with tumor ulceration.

Pyoderma gangrenosum-like ulceration as a presenting feature of pediatric granulomatosis with polyangiitis.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is an anti-neutrophilic cytoplasmic antibody-associated vasculitis affecting small to medium-sized vessels and involves most commonly the kidneys and the respiratory tract. Skin involvement can be seen in up to 50% of children with GPA and is the initial presenting symptom in 7.7%. Pyoderma gangrenosum (PG)-like ulcers are rarely described as a skin manifestation in GPA and very few cases have been reported previously in children. CASE PRESENTATION: We describe 3 new pediatric cases of GPA with PG-like ulcerations. The median age at first symptom was 15 years. Two patients had PG-like ulceration as their initial presentation; additional symptoms eventually led to the diagnosis of GPA 2-24 months later. In 1 case, proteinase 3 (PR3) was negative when first tested, but converted to positive when systemic symptoms emerged; in the other 2 cases PR3 was positive at presentation. All 3 patients had prominent facial lesions. None of the patients responded to treatment with antibiotics or medications commonly used to manage PG, including corticosteroids and cyclosporine. All patients had excellent responses to rituximab. An electronic database literature review was performed and 4 previously reported cases were identified. We assessed the clinical characteristics, serology, and response to treatment of the previously reported and our newly diagnosed cases. CONCLUSION: PG-like ulceration is a rare presentation of pediatric GPA which may precede classic systemic GPA symptoms. The predominance of facial ulcer, granulomatous and neutrophilic inflammation on skin biopsy and lack of response to PG treatments are characteristic of GPA-associated PG-like ulcers. Our review suggests that treatment with rituximab may be needed to improve the skin lesions. Recognizing that PG-like ulcerations can occur in pediatric GPA may result in timely diagnosis, appropriate treatment and improved prognosis.