Clinicopathological features, MCPyV status and outcomes of Merkel cell carcinoma in solid-organ transplant recipients: a retrospective, multicentre cohort study.

BACKGROUND: The proportion of Merkel cell carcinomas (MCCs) in solid-organ transplant recipients (SOTR) harbouring Merkel cell polyomavirus (MCPyV) is unknown, as are factors affecting their outcomes. OBJECTIVE: To describe clinicopathological features of MCC in SOTR, investigate the tumoral MCPyV-status and identify factors associated with tumour outcomes. METHODS: Retrospective, international, cohort-study. MCPyV-status was investigated by immunohistochemistry and polymerase chain reaction. RESULTS: A total of 30 SOTR and 44 consecutive immunocompetent patients with MCC were enrolled. SOTR were younger at diagnosis (69 vs. 78 years, P < 0.001). Thirty-three percent of SOTR MCCs were MCPyV-positive vs. 91% of immunocompetent MCCs (P = 0.001). Solid-organ transplantation was associated with an increased cumulative incidence of progression (SHR: 3.35 [1.57-7.14], P = 0.002), MCC-specific mortality (SHR: 2.55 [1.07-6.06], P = 0.034) and overall mortality (HR: 3.26 [1.54-6.9], P = 0.002). MCPyV-positivity and switching to an mTOR inhibitor (mTORi) after MCC diagnosis were associated with an increased incidence of progression (SHR: 4.3 [1.5-13], P = 0.008 and SHR: 3.6 [1.1-12], P = 0.032 respectively) in SOTR. LIMITATIONS: Retrospective design and heterogeneity of SOTR cohort. CONCLUSIONS: MCPyV appears to play a less prominent role in the aetiopathogenesis of MCC in SOTR. SOTR have a worse prognosis than their immunocompetent counterparts and switching to an mTORi after the diagnosis of MCC does not improve progression.

Treatment of Eosinophilic Annular Erythema: Retrospective multicenter study and literature review.

BACKGROUND: Eosinophilic annular erythema (EAE) is a rare eosinophil-related skin disease which typically manifests with annular erythematous plaques and severe pruritus. Besides the diagnosis, the treatment of EAE is challenging since relevant published data are sparse. METHODS: The aim of this study was to assess the underlying diseases, treatments and outcomes of patients with EAE. To this end, we conducted a retrospective multicenter study and a systematic review of the MEDLINE database. RESULTS: We included 18 patients with EAE followed in 8 centers. The MEDLINE database search yielded 37 relevant publications reporting 55 cases of EAE with 106 treatment sequences. The most common and efficient treatments included topical or systemic corticosteroids, hydroxychloroquine and dapsone. In refractory patients, a combination of systemic corticosteroids with hydroxychloroquine was associated with 88% of complete clinical response. DISCUSSION: To improve the management of EAE patients, we discuss the following treatment strategy: in topical steroid-resistant patients, hydroxychloroquine can be given as first-line systemic treatment. Dapsone, hydroxychloroquine or systemic corticosteroids are second-line options to consider. Last, monoclonal antibodies or JAK inhibitors targeting type 2 inflammation could represent promising last-resort options in refractory patients.

Epidermolysis bullosa simplex generalized severe induces a T helper 17 response and is improved by apremilast treatment.

BACKGROUND: Epidermolysis bullosa simplex generalized severe (EBS-gen sev) is a genetic disorder caused by mutation in the KRT5 or KRT14 genes. Although it is usually considered a mechanical disease, recent data argue for additional inflammatory mechanisms. OBJECTIVES: To assess the inflammation in the skin of patients with EBS-gen sev. METHODS: A first immunohistochemical retrospective study was performed on frozen skin samples from 17 patients with EBS-gen sev. A second multicentre prospective study was conducted on 10 patients with severe EBS-gen sev. Blister fluid and epidermis were processed for immunochemical analysis and quantitative real-time polymerase chain reaction. Cytokine expression was analysed in blister fluid and compared with that in controls. RESULTS: Histological analysis showed a constant dermal perivascular CD4+ lymphocyte infiltrate in skin biopsies of both blister (n = 17) and rubbed skin (n = 5), an epidermal infiltration of neutrophils and eosinophils in 70% of cases, and increased immunostaining for CXCL9 and CXCL10 in blistering skin. High levels of T helper 17 cytokines were detected in lesional skin. Three adult patients with EBS-gen sev were treated with apremilast, with a dramatic improvement of skin blistering and good tolerance. CONCLUSIONS: Our study demonstrates the importance of inflammation in patients with EBS-gen sev and underlines the key role for T helper 17 cells in its pathogenesis. In addition, this study provides promising new therapeutic approaches for this disabling disorder.

Histological classification of cutaneous squamous cell carcinomas with different severity.

Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer. Histology represents the gold standard to confirm the diagnosis of cSCC and is mandatory to determine important findings for tumour grading, such as tumour thickness, depth of invasion, degree of differentiation and histological subtype, perineural and vascular invasion, and assessing tumour margins. In daily clinical practice, the combination of clinical and histological features should be considered when grading the tumours and treating the patients, accordingly. This article aims to provide a structured overview of the most common histological findings of in situ and invasive cSCCs, namely those relevant to their severity, and should facilitate the understanding and evaluation of these results.

Face Transplantation: Partial Graft Loss of the First Case 10 Years Later.

Ten years after the first face transplantation, we report the partial loss of this graft. After two episodes of acute rejection (AR) occurred and completely reversed in the first posttransplantation year, at 90 months posttransplantation the patient developed de novo class II donor-specific antibodies, without clinical signs of AR. Some months later, she developed several skin rejection episodes treated with steroid pulses. Despite rapid clinical improvement, some months later the sentinel skin graft underwent necrosis. Microscopic examination showed intimal thickening, thrombosis of the pedicle vessel, and C4d deposits on the endothelium of some dermal vessels of the facial graft. Flow magnetic resonance imaging of the facial graft showed a decrease of the distal right facial artery flow. Three steroid pulses of 500 mg each, followed by intravenous immunoglobulins (2 g/kg), five sessions of plasmapheresis, and three cycles of bortezomib 1.3 mg/m2 , were administered. Despite rescue therapy with eculizumab, necrosis of the lips and the perioral area occurred, which led to surgical removal of the lower lip, labial commissures, and part of the right cheek in May 2015. In January 2016, the patient underwent conventional facial reconstruction because during the retransplantation evaluation a small-cell lung carcinoma was discovered, causing the patient's death in April 2016.

Chronic Lyme borreliosis associated with minimal change glomerular disease: a case report.

BACKGROUND: There are only few cases of renal pathology induced by Lyme borreliosis in the literature, as this damage is rare and uncommon in humans. This patient is the first case of minimal change glomerular disease associated with chronic Lyme borreliosis. CASE PRESENTATION: A 65-year-old Caucasian woman was admitted for an acute edematous syndrome related to a nephrotic syndrome. Clinical examination revealed violaceous skin lesions of the right calf and the gluteal region that occurred 2 years ago. Serological tests were positive for Lyme borreliosis and skin biopsy revealed lesions of chronic atrophic acrodermatitis. Renal biopsy showed minimal change glomerular disease. The skin lesions and the nephrotic syndrome resolved with a sequential treatment with first ceftriaxone and then corticosteroids. CONCLUSION: We report here the first case of minimal change disease associated with Lyme borreliosis. The pathogenesis of minimal change disease in the setting of Lyme disease is discussed but the association of Lyme and minimal change disease may imply a synergistic effect of phenotypic and bacterial factors. Regression of proteinuria after a sequential treatment with ceftriaxone and corticosteroids seems to strengthen this conceivable association.

Comparative histological analysis of drug-induced maculopapular exanthema and DRESS.

BACKGROUND: Cutaneous adverse drug reactions frequently present as a benign maculopapular exanthema (MPE) with a rapid healing. Sometimes systemic signs are present, which could represent a more severe or systemic MPE (sMPE) or even be the initial phase of a drug reaction with eosinophilia and systemic symptoms (DRESS). Histopathology associated with MPE, sMPE and DRESS has not been well characterized. OBJECTIVES: To study the cutaneous histopathological changes associated with MPE, sMPE and DRESS. METHODS: A retrospective clinicopathological analysis of 13 cases of MPE, 13 of sMPE and 45 of DRESS, collected in one centre from 2005 to 2013. RESULTS: The number of histopathological changes per section increased gradually from MPE to sMPE and DRESS. Prevalence of spongiosis, dermal lymphocytes, eosinophils and neutrophils did not differ between MPE, sMPE and DRESS. Keratinocyte damage, rare in MPE, was regularly found in sMPE and frequent in DRESS. The density of the inflammatory infiltrate increased progressively from MPE to sMPE and DRESS. Atypical lymphocytes were absent in MPE, present in sMPE and more frequent in DRESS. Deep dermal involvement and leukocytoclastic vasculitis were only observed in DRESS. LIMITATIONS: This was a retrospective study. CONCLUSIONS: Numerous histopathological changes per section in drug-induced exanthema should alert for a more severe form of cutaneous adverse drug reactions, i.e. DRESS.

Reticular erythematous mucinosis: histopathological and immunohistochemical features of 25 patients compared with 25 cases of lupus erythematosus tumidus.

BACKGROUND AND OBJECTIVES: Reticular erythematous mucinosis (REM) and lupus erythematosus tumidus (LET) share similarities. However, to our knowledge no study extensively compared the histological features of these two conditions. The aim of this study is to compare the histological and immunohistochemical features of REM and LET. METHODS: We evaluated epidermal thickness, hyperkeratosis, dermo-epidermal junction changes, interstitial mucin deposition, vessel dilatation and pattern, type and density of the inflammatory infiltrate in 25 cases of REM and LET. Anti-CD3, anti-CD20, anti-CD68, anti-CD4, anti-CD8, anti-CD123, anti-CD2AP, anti-IgG and anti-C3 antibodies were tested in a subset of patients. RESULTS: Both diseases are characterized by perivascular dermal infiltrates of lymphocytes mainly CD4+ positive and increased dermal mucin. However, REM tended to show more scattered and more superficial lymphocytes with more superficial mucin and to have less frequent immunoglobulin and complement depositions along the dermo-epidermal junction. Plasmacytoid dendritic cells (PDCs) were less represented in REM, and were mainly found as single cells differently from LET. CONCLUSIONS: REM and LET present some differences in the infiltrate, including PDCs, the mucin deposition and the immunoreactant deposition at the dermo-epidermal junction that justify the distinction of the two diseases and suggest different pathogenetic mechanisms.

Drug reaction with eosinophilia and systemic symptoms (DRESS): clinicopathological study of 45 cases.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare and severe adverse drug reaction. Large detailed studies of histopathological features of DRESS are sparse and suggest an association between keratinocyte damage and the severity of visceral involvement. OBJECTIVES: To describe the dermatopathological features in a large series of DRESS and their possible association with clinical features and the severity of the disease. METHODS: A retrospective analysis of the clinicobiological and dermatopathological features in a monocentric cohort of patients with DRESS. RESULTS: From January 2005 to January 2013, 45 patients were validated as probable or definite cases of DRESS. The median age was 64 years (range 3-87). The most frequent clinical and biological features included: fever ≥38.5°C (95%), facial oedema (72%), enlarged lymph nodes (51%), visceral involvement (75%), blood eosinophilia (97%) and atypical lymphocytes (82%). Severe DRESS occurred in 24% and a fatal outcome in 6% of patients. Histopathological analysis showed that no specific histopathological pattern was characteristic for DRESS. However, several changes in different cutaneous compartments were observed in 2 of 3 of cases. Spongiosis (55%) and keratinocyte damage (53%) were the most common epidermal changes. Spongiosis was associated with non-severe DRESS (P = 0.041) whereas confluent keratinocyte necrosis correlated with severe DRESS (P = 0.011). Vascular changes were frequent (88%). A moderate dermal perivascular lymphocytic infiltrate was invariably present, containing eosinophils, neutrophils and/or atypical lymphocytes in 57% of cases. CONCLUSIONS: Epidermal changes are indicative for the severity of DRESS.

Primary cutaneous posttransplant lymphoproliferative disorders in solid organ transplant recipients: a multicenter European case series.

Primary cutaneous posttransplant lymphoproliferative disorders (PTLD) are rare. This retrospective, multicenter study of 35 cases aimed to better describe this entity. Cases were (re)-classified according to the WHO-EORTC or the WHO 2008 classifications of lymphomas. Median interval between first transplantation and diagnosis was 85 months. Fifty-seven percent of patients had a kidney transplant. Twenty-four cases (68.6%) were classified as primary cutaneous T cell lymphoma (CTCL) and 11 (31.4%) as primary cutaneous B cell PTLD. Mycosis fungoides (MF) was the most common (50%) CTCL subtype. Ten (90.9%) cutaneous B cell PTLD cases were classified as EBV-associated B cell lymphoproliferations (including one plasmablastic lymphoma and one lymphomatoid granulomatosis) and one as diffuse large B cell lymphoma, other, that was EBV-negative. Sixteen (45.7%) patients died after a median follow-up of 19.5 months (11 [68.8%] with CTCL [6 of whom had CD30(+) lymphoproliferative disorders (LPD)] and 5 [31.2%] with cutaneous B cell PTLD. Median survival times for all patients, CTCL and cutaneous B cell PTLD subgroups were 93, 93, and 112 months, respectively. Survival rates for MF were higher than those for CD30(+) LPD. The spectrum of primary CTCL in organ transplant recipients (OTR) is similar to that in the general population. The prognosis of posttransplant primary cutaneous CD30(+) LPD is worse than posttransplant MF and than its counterpart in the immunocompetent population. EBV-associated cutaneous B cell LPD predominates in OTR.

Reticular erythematous mucinosis: a review of patients' characteristics, associated conditions, therapy and outcome in 25 cases.

BACKGROUND: Reticular erythematous mucinosis (REM) is an uncommon disease, the nosology and specific characteristics of which are controversial because most reports deal with single cases or small series. OBJECTIVES: To describe the characteristics of patients with REM regarding demographics, clinical and pathological features, comorbidities, treatment and course. METHODS: A retrospective and prospective study was conducted on 25 patients diagnosed with REM in the setting of university-affiliated dermatology departments and dermatopathology centres. RESULTS: Of the 25 patients with REM, 16 were women (sex ratio 2 : 1) and the mean age was 46 years. The roles of sun exposure and oral contraceptives were ambiguous. Associated diseases included hypertension (n = 4), malignancies (n = 3), autoimmune diseases (n = 3) and Borrelia infection (n = 1). Immunological studies (including serology and direct immunofluorescence) were noncontributory. The response to antimalarial treatment was good in > 80% of cases. Worsening or recurrence of the lesion after treatment discontinuation, or in the course of the disease, occurred in 31% of patients. CONCLUSIONS: We present the largest REM case series to date. The reticular pattern with involvement of the midline of the chest and back, the predilection for middle-aged women, the controversial relationship with photosensitivity and the possible association with other conditions such as malignancies and thyroid dysfunctions are the main characteristics that makes REM a recognizable disease.

[In vivo reflectance confocal microscopy in dermatology: a proposal concerning French terminology]. / La microscopie confocale par réflectance in vivo en dermatologie : proposition de terminologie en langue française.

BACKGROUND: Reflectance confocal microscopy (RCM) is a recently introduced non-invasive imaging technique allowing real-time examination of the skin in vivo. Whereas a substantial literature concerning RCM exists in English, so far there is no official terminology in French, despite the fact that an ever-growing number of French-speaking dermatologists now use this new imaging technique. The aim of the present study is to propose a French terminology for RCM in order to allow French-speaking dermatologists to communicate in a precise and homogeneous language on this topic. METHODS: A group of French-speaking dermatologists with solid experience of RCM, members of the Non-invasive Cutaneous Imaging group of the French Society of Dermatology, endeavored to suggest terms in French concerning RCM. Each group member dealt with a specific paragraph. The members exchanged comments via email and the terminology was finalized during a meeting of the group members in Paris in June 2012. RESULTS: Descriptive terms referring to the RCM aspects of normal and diseased skin were proposed. Some of these already existed, being used in routine dermatopathology, while other specific terms were created or adapted from the English terminology. CONCLUSION: This terminology will allow French-speaking dermatologists using RCM to communicate their findings in a homogeneous language. It may be enriched in the future by the introduction of additional terms describing new aspects of both normal and, especially, diseased skin.

Cutaneous bacillary angiomatosis in renal transplant recipients: report of three new cases and literature review.

Bacillary angiomatosis (BA) is a rare vasculoproliferative disorder due to Bartonella henselae (BH) or Bartonella quintana. It can involve many organs, including the skin, and has been mainly reported in patients with acquired immunodeficiency syndrome. In organ transplant recipients (OTR), this disorder remains misdiagnosed and therapeutic guidelines are nonexistent. We report 3 cases of BA with skin involvement in OTR and review similar cases from the literature. BA manifests on the skin with violaceous lesions mimicking Kaposi sarcoma, and is associated with fever, lymphadenopathy, and liver, spleen, or lung nodules. Bartonellosis infections in OTR are due to BH, the agent causing cat-scratch disease (CSD), but BA comprises histologically a prominent vascular proliferation, which is usually lacking in CSD. Cultures and serologic tests are poorly reliable for the diagnosis, which relies on demonstration of BH within the lesions. A history of cat exposure exists in most cases and pediatric OTR are at higher risk. Prevention consists of regular use of a flea-control product in cats and prompt cleaning of scratches. Our cases highlight several original features of this rare condition, which could potentially improve the management of BA in OTR.

Long-term follow-up in composite tissue allotransplantation: in-depth study of five (hand and face) recipients.

Composite tissue allotransplantations (CTAs) have clinically shown little, if any, evidence of chronic rejection. Consequently, the effect of chronic rejection on bones, joints, nerves, muscles, tendons and vessels may still have undescribed implications. We thoroughly assessed all allograft structures by histology, magnetic resonance imaging, ultrasonography and high resolution peripheral quantitative computed tomography scan in four bilateral hand-grafted patients (10, 7, 3 and 2 years of follow-up, respectively) and in one facial allotransplantation (5 years of follow-up). All the recipients presented normal skin structure without dermal fibrosis. Vessels were patent, without thrombosis, stenosis or intimal hyperplasia. Tendons and nerves were also normal; muscles showed some changes, such as a variable degree of muscular hypotrophy, particularly of intrinsic muscles, accompanied by fatty degeneration that might be related to denervation. In the majority of hand-grafted patients graft radius and recipient tibia showed a decrease in trabecular density, although in the graft radius the alterations also involved the cortices. No deterioration of graft function was noted. In these cases of CTA no signs of chronic graft rejection have been detected. However, the possibility that chronic rejection may develop in CTA exists, highlighting the necessity of close continuous follow-up of the patients.

Pure apocrine nevus: immunohistochemical study of a new case and literature review.

Apocrine nevi are benign adnexal cutaneous hamartomas characterized by localized hyperplasia of mature apocrine sweat glands (ASG). Although ASG proliferation can be found in a number of acquired or congenital adnexal skin tumors, pure apocrine nevi are exceedingly rare. We present herein a new typical case of this tumor that was studied immunohistochemically, and review the relevant literature in order to delineate its clinicopathological features.

Circumscribed palmo-plantar hypokeratosis: a disease of desquamation? Immunohistological study of five cases and literature review.

BACKGROUND: Circumscribed palmoplantar hypokeratosis (CPH) is a recently recognized, rarely reported dermatosis that shows characteristic clinicopathological features; however, its pathogenesis remains unknown. OBJECTIVE: The aim of this study was to get further insight into the pathogenesis of CPH. METHODS: An immunohistological study was performed on five cases of CPH to investigate the expression of several epidermal proliferation and differentiation proteins, with emphasis on those involved in corneocyte desquamation [including corneodesmosin, kallikrein 5 and lympho-epithelial Kazal type inhibitor (LEKTI)]. RESULTS: In three of five cases, a decreased expression of LEKTI, corneodesmosin and filaggrin was found, along with an increased expression of kallikrein 5 and keratin 6. The expression of several other antigens (including involucrin, Ki67, p63, CD138/syndecan I, EGF-R) did not present a consistently different pattern as compared with the unaffected epidermis. CONCLUSION: The immunohistopathologic features of CPH suggest that an altered (accelerated) corneocyte desquamation process could be the main pathological mechanism underlying the development of lesions.

Premalignant circumscribed palmar hypokeratosis: a new form of circumscribed palmar hypokeratosis? Case report and literature review.

Circumscribed palmoplantar hypokeratosis (CPH) is a recently described dermatosis of unknown origin, of which 46 cases have been published so far. CPH affects predominantly adult women. It presents clinically with a sharply circumscribed annular erythematous depressed plaque rimmed by a slightly hyperkeratotic border, localized usually over the thenar or hypothenar eminences of the palm, less commonly on the soles. Histopathologically, it is characterized by an abrupt decrease in the horny layer thickness, forming a sharp stair between normal and involved skin. We report herein a new patient with CPH who presented an associated aspect of actinic keratosis, a hitherto unreported finding. This case suggests that CPH can undergo malignant transformation, probably as a result of actinic damage. On this occasion, a complete literature review of CPH is presented.