Post-transplant lymphoproliferative disorder with cutaneous involvement: A series of four cases.

BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are lymphoid proliferations associated with post-transplant immunosuppression. Most originate from B cells and are associated with Epstein-Barr virus (EBV) infection. Although extranodal involvement is common, cutaneous presentation is rare. OBJECTIVE: To report and characterize cutaneous manifestations of PTLD from clinical, histopathologic, and immunohistochemistry standpoints. METHODS: Patients' information was obtained retrospectively by reviewing medical records. Skin biopsies were submitted to histological and immunohistochemistry analysis, and EBV detection was performed by in situ hybridization and polymerase chain reaction (PCR) analysis. Staging examinations were included. A literature review of reported cutaneous PTLD cases was performed. RESULTS: We describe two cases of primary cutaneous and 2 cases of systemic PTLD with secondary cutaneous manifestations. All had late onset disease, which presented at least 6 years after transplantation. Histopathologic findings were compatible with monomorphic PTLD in three cases and plasmacytic hyperplasia in one case. EBV was detected in two patients. Both patients with systemic disease had fatal outcome, and those with primary cutaneous involvement responded to treatment. LIMITATIONS: Due to the rare incidence of cutaneous manifestation of PTLD, the analysis of a large number of cases was not possible. CONCLUSION: Although rare, PTLD should be considered in the differential diagnosis of late onset cutaneous complications post-renal transplant.

Reassessing Melanonychia Striata in Phototypes IV, V, and VI Patients.

BACKGROUND: Racial melanonychia striata is a nail plate dyschromia described as a gray coloration of the background in dermatoscopy and hypermelanosis in histology. However, many cases with brown or black coloration of the background in the dermatoscopic examination have been followed. OBJECTIVE: Evaluate racial melanonychia striata dermatoscopical patterns and histological diagnosis in Fitzpatrick skin Types IV, V, or VI population. MATERIALS AND METHODS: 482 Fitzpatrick skin Types IV, V, or VI patients, between 19 and 72 years of age, were clinically evaluated and underwent nail plate dermatoscopic examination. Fifty-eight patients presenting melanonychia striata and dermatoscopic patterns with brown or black coloration of the background were submitted to a nail matrix biopsy. When occurring in more than 1 digit, biopsy was performed in the lesion with the darkest coloration presented in dermatoscopy. RESULTS: All skin Types IV, V, or VI patients who had melanonychia striata, with brown or black coloration of the background in the dermatoscopic examination, revealed histopathological analysis compatible with hypermelanosis. CONCLUSION: Racial melanonychia in skin Types IV, V, or VI patients, resulting from hypermelanosis, may present brown or black coloration of the background in the dermatoscopic examination.

A comparative exploration of immunohistochemical markers in patients with papulopustular rosacea undergoing treatment with oral isotretinoin versus doxycycline.

BACKGROUND: Rosacea is a chronic inflammatory disease, and doxycycline is a widely recommended treatment for it due to its anti-inflammatory action. Oral isotretinoin reduces sebaceous gland activity and modulates toll-like receptors, reducing inflammation. Our aim was to investigate the effect of these two drugs on the expression of cutaneous immunohistochemical biomarkers related to etiopathogenic factors involved in rosacea. METHODS: We conducted a randomized, comparative, and evaluator-blinded trial, including 40 participants with moderate and severe papulopustular and ocular rosacea. Participants were treated with doxycycline (DOXY) 100 mg or isotretinoin (ISO) 0.3 mg/kg daily. Immunohistochemistry at baseline and after 4 months was used to demonstrate the expression of the biomarker on the affected skin. RESULTS: The following changes were detected: a reduction in the vessel count after using VEGF with DOXY (P = 0.010); a decrease in VEGF intensity with ISO (P < 0.001) and DOXY (P = 0.020); a reduction of nitric oxide synthase enzyme with both drugs in the inflammatory infiltrate (ISO P < 0.001; DOXY P = 0.003); however, only with ISO was there a significant (P = 0.030) decrease at the level of the sebaceous glands, indicating a reduction of nitric oxide synthesis; a reduction of TRPV-1 expression at the level of the sebaceous glands was observed only with DOXY (P = 0.041); a decrease of cathelicidin LL37 expression, a key antimicrobial peptide in the etiopathogenesis of rosacea, was noted with both drugs, although at the level of sebaceous glands, only with DOXY (P = 0.007). CONCLUSIONS: Oral isotretinoin and doxycycline have modified the expression of cutaneous biomarkers related to rosacea etiopathogenesis, demonstrating their role in controlling inflammatory and vascular processes.

Skin manifestations associated with COVID-19.

This article will address the main aspects of skin manifestations associated with COVID-19, based on a review of the literature published to date. Since the beginning of the pandemic, more than 1,500 articles have been published on the subject. Regarding the pathophysiology, it is believed that the same mechanisms responsible for the disease in the main target organs also act in the skin, although they are not yet fully elucidated. The actual frequency of dermatological manifestations remains uncertain - it can range from 0.2% to 45%, being close to 6% in systematic reviews. Pioneering studies of large case series conducted in European countries and the USA provide the first information on the main skin manifestations associated with COVID-19 and propose classifications regarding their clinical presentation, pathophysiology, as well as their frequencies. Although there is yet no consensus, maculopapular eruptions are considered the most frequent presentations, followed by erythema pernio-like (EPL) lesions. Manifestations such as urticaria, vesicular conditions and livedo/purpura/necrosis are rare. The time of onset, severity, need for specific treatment and prognosis vary according to the clinical presentation pattern. The increasing histopathological description of skin conditions can contribute to the diagnosis, as well as to the understanding of the pathophysiology. Also, in the dermatological field, the relationship between COVID-19 and androgens has been increasingly studied. Despite all the generated knowledge, the actual biological meaning of skin manifestations remains uncertain. Therefore, the exclusion of the main differential diagnoses is essential for the correlation between skin manifestation and COVID-19.

Cutaneous chromoblastomycosis mimicking melanoma in a renal transplant recipient.

Chromoblastomycosis is a primary implantation mycosis caused by melanized fungi. It affects mainly populations from remote and rural areas, and may cause significant morbidity and mortality. A 69-year-old kidney transplant recipient woman presented with a dark nodule on the first left toe and a satellite lesion. Dermoscopic exam showed multiple clustered black dots, blackened homogenous area and chrysalides, which led to the diagnostic hypothesis of melanoma. Histopathological examination was compatible with chromoblastomycosis.

Therapeutic management of subcutaneous phaeohyphomycosis and chromoblastomycosis in kidney transplant recipients: a retrospective study of 82 cases in a single center.

BACKGROUND: Melanized fungi are a distinct group of pathogens that cause infections like chromoblastomycosis and phaeohyphomycosis, especially in a state of immunosuppression including solid organ transplant recipients. Guidelines for the treatment of these infections are lacking, and there is no available standard recommendation. OBJECTIVE: To evaluate the therapeutic aspects of subcutaneous melanized fungal infections in kidney transplant recipients. METHODS: A retrospective medical record was performed for kidney transplant recipients with melanized fungal infection evaluated in a single institution from January 1996 to December 2018. RESULTS: Eighty-two episodes were noticed in our series. The treatment of subcutaneous phaeohyphomycosis was managed by surgical excision without antifungal therapy in 34 cases (34/68; 50%), and the association of both methods occurred in 18 cases (18/68; 26.5%). A complete surgical excision without antifungal therapy was observed in six (6/14; 42.9%) episodes of chromoblastomycosis, and combined treatment was possible in three (3/14; 21.4%) cases. Five episodes of chromoblastomycosis and 16 episodes of phaeohyphomycosis were managed only with antifungal therapy. CONCLUSION: Management depends on the dermatologic lesion, immunosuppression condition, and anatomical cleavage plane. The sample size is still small in order to dictate a guideline, but it can be hard to execute a larger study given the rarity of this group of infections.

Rosettes in T-cell pseudolymphoma: a new dermoscopic finding.

Rosettes are small white structures visible with polarized light dermoscopy, whose exact morphological correlation is not yet defined. These small shiny structures are found in several conditions such as scarring, dermatofibroma, molluscum contagiosum, squamous cell carcinoma, basal cell carcinoma, melanoma, melanocytic nevus, discoid lupus erythematosus, and papulopustular rosacea. In this novel report, the authors describe the presence of rosettes in a T-cell pseudolymphoma lesion.

Lymphocytic thrombophilic arteritis with lower-limb ulcers.

Lymphocytic thrombophilic arteritis is a recently described entity, histopathologically characterized by lymphocytic vasculitis that affects the arterioles of the dermo-hypodermic junction, associated with deposition of fibrin and a luminal fibrin ring. A 49-year-old female patient presented with achromic maculae and a well-defined ulcer on the medial aspect of the left lower limb. The biopsy showed intense inflammatory infiltrate in the papillary dermis with a predominance of lymphocytes, and medium-caliber vessels surrounded by mononuclear infiltrates in the deep reticular dermis. Masson's trichrome staining showed intense destruction of the muscle layer of the vascular wall and a fibrin ring. Good clinical response was attained with azathioprine. The authors believe that the ulceration might be another clinical presentation or represent an atypical progression of this condition.

Cutaneous protothecosis in kidney transplant recipient.

Protothecosis is a rare condition caused by the aclorophylated algae of the genus Prototheca. In humans, protothecosis, caused mainly by P. wickerhamii, manifests itself in three forms: cutaneous, articular and systemic. It can occur in both immunocompetent and immunosuppressed individuals, being much more common in the latter. We present a new case of protothecosis in Brazil in a kidney transplant recipient.

Pemphigus vulgaris.

Pemphigus vulgaris is a chronic autoimmune bullous dermatosis that results from the production of autoantibodies against desmogleins 1 and 3. It is the most frequent and most severe form of pemphigus, occurring universally, usually between 40 and 60 years of age. It usually begins with blisters and erosions on the oral mucosa, followed by lesions on other mucous membranes and flaccid blisters on the skin, which can be disseminated. There is a clinical variant, pemphigus vegetans, which is characterized by the presence of vegetating lesions in the large folds of the skin. Clinical suspicion can be confirmed by cytological examination, histopathological examination, and direct and indirect immunofluorescence tests. The treatment is performed with systemic corticosteroids, and immunosuppressive drugs may be associated, among them azathioprine and mycophenolate mofetil. More severe cases may benefit from corticosteroids in the form of intravenous pulse therapy, and recent studies have shown a beneficial effect of rituximab, an anti-CD20 immunobiological drug. It is a chronic disease with mortality around 10%, and septicemia is the main cause of death. Patients need long-term and multidisciplinary follow-up.

Study of tissue inflammatory response in different mice strains infected by dematiaceous fungi Fonsecaea pedrosoi.

BACKGROUND: Diseases caused by melanized fungi include mycetoma, chromoblastomycosis and phaeohyphomycosis. This broad clinical spectrum depends on the dynamic interactions between etiologic agent and host. The immune status of the host influences on the development of the disease, as, an exemple. phaeohyphomicosis is more frequently observed in immunocompromised patients. OBJECTIVES: Examine the histological inflammatory response induced by Fonsecaea pedrosoi in several different strains of mice (BALB/c, C57BL/6, Nude and SCID, and reconstituted Nude). METHODS: Fonsecaea pedrosoi was cultivated on agar gel and a fragment of this gel was implanted subcutaneously in the abdominal region of female adult mice. After infection has been obtained, tissue fragment was studied histopathologically. RESULTS: There were significant changes across the strains, with the nodular lesion more persistent in Nude and SCID mice, whereas in immunocompetent mice the lesion progressed to ulceration and healing. The histopathological analysis showed a significant acute inflammatory reaction which consisted mainly of neutrophils in the initial phase that was subsequently followed by a tuberculoid type granuloma in immunocompetent mice. STUDY LIMITATIONS: There is no a suitable animal model for chromoblastomycosis. CONCLUSIONS: The neutrophilic infiltration had an important role in the containment of infection to prevent fungal spreading, including in immunodeficient mice. The fungal elimination was dependent on T lymphocytes. The re-exposure of C57BL/6 mice to Fonsecaea pedrosoi caused a delay in resolving the infection, and appearance of muriform cells, which may indicate that re-exposure to fungi, might lead to chronicity of infection.

Lenalidomide in the management of eosinophilic dermatosis of hematological malignancy.

Eosinophilic dermatosis of hematological malignancy is a paraneoplastic skin eruption associated with chronic lymphocytic leukemia and other B-cell malignancies. It clinically resembles an insect bite reaction and it can precede the symptoms of the hematological malignancy or be related to a more aggressive course. Different treatments have been proposed, but partial response and recurrence are frequent. Herein, we describe a case of eosinophilic dermatosis associated with mantle cell lymphoma with remission after lenalidomide therapy.

Hailey-Hailey disease: clinical, diagnostic and therapeutic update

Abstract Hailey-Hailey disease is a rare genodermatosis described in 1939, with an autosomal dominant inheritance pattern, characterized by compromised adhesion between epidermal keratinocytes. It has an estimated prevalence of 1/50,000, with no gender or race predilection. It results from a heterozygous mutation in the ATP2C1 gene, which encodes the transmembrane protein hSPA1C, present in all tissues, with preferential expression in keratinocytes. Mutations in the ATP2C1 gene cause changes in the synthesis of junctional proteins, leading to acantholysis. It usually begins in adulthood, with isolated cases at the extremes of life. It manifests as vesico-bullous lesions mainly in the flexural areas, which develop into erosions and crusts. Chronic lesions may form vegetative or verrucous plaques. Pruritus, a burning feeling and pain are common. It evolves with periods of remission and exacerbation, generally triggered by humidity, friction, heat, trauma and secondary infections. The diagnosis is based on clinical and histopathological criteria: marked suprabasal acantholysis, loosely joined keratinocytes, giving the appearance of a "dilapidated brick wall", with a few dyskeratotic cells. The acantholysis affects the epidermis and spares the adnexal epithelia, which helps in the differential diagnosis with pemphigus vulgaris. Direct immunofluorescence is negative. The main differential diagnoses are Darier disease, pemphigus vegetans, intertrigo, contact dermatitis, and inverse psoriasis. There is no cure and the treatment is challenging, including measures to control heat, sweat and friction, topical medications (corticosteroids, calcineurin inhibitors, antibiotics), systemic medications (antibiotics, corticosteroids, immunosuppressants, retinoids and immunobiologicals) and procedures such as botulinum toxin, laser and surgery. There is a lack of controlled clinical trials to support the choice of the best treatment.

Adult linear IgA bullous dermatosis: report of three cases.

Linear immunoglobulin A bullous dermatosis is a rare autoimmune disease that usually has an excellent prognosis in childhood; however, its control is more difficult in adults. It presents heterogeneous clinical manifestations and is frequently confused with other bullous diseases such as bullous pemphigoid and Duhring's dermatitis herpetiformis. Dermatologists' awareness of this disease contributes to early diagnosis and appropriate treatment. We thus report three cases of linear immunoglobulin A dermatosis in adults.

Coexistence of chronic cutaneous lupus erythematosus and frontal fibrosing alopecia.

Lupus erythemathosus is a chronic, relapsing disease with acute, subacute, and chronic lesions. Effluvium telogen occurs in the setting of systemic activity of the disease, and cicatricial alopecia results from discoid lesionsin on the scalp. Other types of alopecia, like alopecia areata, may rarely be found in lupus. Frontal fibrosing alopecia is characterized by frontotemporal hairline recession and eybrow loss. Histophatologically, it cannot be differentiated from lichen planopilaris.It is controversial whether frontal fibrosing alopecia is a subtype of lichen planopilaris.. A pacient with chronic lichenoid lupus erythematosus is described with clinical, histophatological and dermoscopic features of frontal fibrosing alopecia.We have not been able to find in the literature cases of frontal fibrosing alopecia as a clinical manifestation of lupus.

Disseminated fusariosis with cutaneous involvement in hematologic malignancies: report of six cases with high mortality rate.

Fusariosis is due to inhalation or direct contact with conidia. Clinical presentation depends on host's immunity and can be localized, focally invasive or disseminated. Given the severity of this infection and the possibility for the dermatologist to make an early diagnosis, we report six cases of patients with hematologic malignancies, who developed febrile neutropenia an skin lesions suggestive of cutaneous fusariosis. All patients had skin cultures showing growth of Fusarium solani complex, and they received amphotericin B and voriconazole. As this infection can quickly lead to death, dermatologists play a crucial role in diagnosing this disease.

A case of pigmented Bowen's disease.

Pigmented Bowen's disease is a rare subtype of Bowen's disease. Clinically it presents as a slow-growing, well-defined, hyperpigmented plaque, and should be included as a differential diagnosis of other pigmented lesions. The authors describe a challenging case of pigmented Bowen's disease with non-diagnostic dermscopy findings.

Disseminated cryptococcosis with skin lesions: report of a case series.

Cryptococcosis is a common fungal infection in immunocompromised patients, caused by genus Cryptococcus, presenting with meningitis, pneumonia, and skin lesions. Cutaneous presentation can be varied, but specifically in solid organ transplant recipients (iatrogenically immunocompromised), cryptococcosis should always be considered in the differential diagnosis of cellulitis-like lesions, since the delay in diagnosis leads to worse prognosis and fatal outcome. We report four cases of cryptococcosis with cutaneous manifestation not only for its rarity, but also to emphasize the important role of the dermatologist in the diagnosis of this disease.