CLDN1 Arg81His founder variant causes ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis (ILVASC) syndrome in Moroccan Jews.

Neonatal ichthyosis and sclerosing cholangitis syndrome (NISCH), also known as ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis (ILVASC), is an extremely rare disease of autosomal recessive inheritance, resulting from loss of function of the tight junction protein claudin-1. Its clinical presentation is highly variable, and is characterized by liver and ectodermal involvement. Although most ILVASC cases described to date were attributed to homozygous truncating variants in CLDN1, a single missense variant CLDN1 p.Arg81His, associated with isolated skin ichthyosis phenotype, has been recently reported in a family of Moroccan Jewish descent. We now describe seven patients with ILVASC, originating from four non consanguineous families of North African Jewish ancestry (including one previously reported family), harboring CLDN1 p.Arg81His variant, and broaden the phenotypic spectrum attributed to this variant to include teeth, hair, and liver/bile duct involvement, characteristic of ILVASC. Furthermore, we provide additional evidence for pathogenicity of the CLDN1 p.Arg81His variant by transmission electron microscopy of the affected skin, revealing distorted tight junction architecture, and show through haplotype analysis in the vicinity of the CLDN1 gene, that this variant represents a founder variant in Jews of Moroccan descent with an estimated carrier frequency of 1:220.

Mycosis Fungoides in Solid-Organ Transplant Recipients: A Multicenter Retrospective Cohort Study.

BACKGROUND: Mycosis fungoides (MF) in solid-organ transplant recipients (SOTRs) is rare, with limited data on disease characteristics. OBJECTIVE: The aim was to study the characteristics of MF in SOTRs with an emphasis on the immunosuppressive therapy. METHODS: A retrospective cohort of patients diagnosed with MF, who were also SOTRs, were followed at 3 cutaneous lymphoma outpatient clinics, between January 2010 and February 2022. RESULTS: Ten patients were included (7 male; median ages at transplantation and at diagnosis of MF were 33 and 48 years, respectively; 40% were diagnosed before the age of 18 years). Median time from transplantation to diagnosis of MF was 8 years (range 0.5-22). Transplanted organs and immunosuppressive treatments included: liver (n = 5; 4 treated with tacrolimus, 1 with tacrolimus and prednisone), kidney (n = 3), liver and kidney (n = 1), and heart (n = 1), all treated with mycophenolic acid, tacrolimus, and prednisone. Nine had early-stage MF (IA - 4, IB - 5; 40% with early folliculotropic MF), treated with skin-directed therapies, in 2 combined with acitretin, achieving partial/complete response. One patient had advanced-stage MF (IIIA) with folliculotropic erythroderma, treated with ultraviolet A and narrow-band ultraviolet B with acitretin, achieving partial response. Immunosuppression was modified in 3. At last follow-up (median 4 years, range 1-8), no stage progression was observed; 5 had no evidence of disease, 5 had active disease (IA/IB - 4, III - 1). CONCLUSIONS: MF in SOTRs is usually diagnosed at an early stage, with overrepresentation of folliculotropic MF, and of children. Immunosuppressive therapy alterations, not conducted in most patients, should be balanced against the risk of organ compromise/rejection. Disease course was similar to MF in immunocompetent patients, during the limited time of follow-up.

New Insights into Macular Type of Primary Cutaneous B-Cell Lymphoma: Extension of the Clinical and Histopathological Patterns.

BACKGROUND: Primary cutaneous B-cell lymphoma (PCBCL) classically presents with papules, plaques, and nodules/tumors. Previous reports of PCBCL manifesting with macular lesions are scarce and focused on primary cutaneous follicle-center cell lymphoma (PCFCL). OBJECTIVES: The objective of this study was to report our experience with PCBCL presenting with erythematous macules. METHODS: Patients with low-grade PCBCL manifesting with erythematous patches, diagnosed and managed between January 2000 through December 2019 at 2 tertiary cutaneous-lymphoma outpatient clinics, were included. Clinical data were retrospectively collected, and biopsy specimens of the macules, and if present of the typical nodular/tumoral lesions, were reviewed. RESULTS: There were 14 patients, aged 16-67 years, 8 had PCFCL and 6 marginal zone lymphoma (PCMZL). All had 1-15 cm erythematous macules, mimicking: interstitial granuloma annulare/vascular tumors/early-stage folliculotropic mycosis fungoides, or presenting with figurate erythema or livedo reticularis-like/net-like pattern. In 3 patients, macules were the presenting lesions, in 2 as the sole manifestation, whereas in 12 patients, typical PCBCL lesions were observed during disease course. The macules showed in all, superficial and deep perivascular infiltrates, and in most, periadnexal infiltrates. Micronodules were observed in 11 specimens, with nodular infiltrates also observed in 4. B cells comprised the majority of the lymphocytes in only 4. Seven of 11 cases tested showed immunoglobulin heavy chain monoclonality. CONCLUSIONS: PCMZL and PCFCL may manifest with erythematous macules. Physicians should be aware of this unusual manifestation of low-grade PCBCL, which may represent a clinicopathological diagnostic pitfall.

The Risk of Internal Malignancy Following a Prior Diagnosis of Non-Melanoma Skin Cancer in Solid Organ Transplant Recipients.

BACKGROUND: Solid organ transplant recipients (SOTRs) are at increased risk for both skin and internal malignancies (IM). The risk of IM after the occurrence of non-melanoma skin cancer (NMSC) has been studied in the general population but very little is known about this association in SOTRs. OBJECTIVES: To evaluate the risk of IM following a prior diagnosis of post transplantation NMSC in SOTRs. METHODS: This single center retrospective cohort study included a study population of 329 SOTRs from Rabin Medical Center who had a post-transplant diagnosis of skin malignancy, internal malignancy, or both from 2012 to 2018. RESULTS: In total, 135 (41.03%) SOTRs were diagnosed with IM without a preceding diagnosis of NMSC while only 42 (12.76%) patients diagnosed with IM had a preceding diagnosis of NMSC. SOTRs with a diagnosis of NMSC showed a significantly decreased risk of developing subsequent IM (hazard ratio [HR] 0.64, 95% confidence interval [95%CI] 0.44-0.94, P = 0.02) compared to those without a prior NMSC diagnosis. Liver and lung transplant patients showed a significantly decreased risk of developing subsequent IM after a diagnosis of NMSC (HR 0.09 and 0.43, respectively). When stratified by type of IM, only patients who were diagnosed with a hematological malignancy had a significantly lower risk of developing this malignancy if they had a prior NMSC (HR 0.26). CONCLUSIONS: The findings of this study suggest a protective effect of NMSC on subsequent IM in the organ transplant population.

The Course of Mycosis Fungoides under Cytokine Pathway Blockers: A Multicentre Analysis of Real-life Clinical Data.

Literature regarding the effect of biologics on the course of mycosis fungoides (MF) is scarce. This multicentre study analysed retrospective data on 19 patients with MF, who were treated with biologics; 12 for inflammatory conditions coexisting with MF, and 7 for MF misdiagnosed as an inflammatory skin disease. Eight patients were treated with anti-tumour necrosis factor-α-monotherapy; 6 had early-stage MF, in 3 patients MF preceded and in 3 MF was diagnosed after initiation of biologics, with no stage-progression or with stable disease, respectively (median treatment time concurrent with MF 57 months). Two patients had advanced stage MF: IIB, treated for 15 months with no stage-progression, and IVA1, treated for 8 months, died of disease 10 months later. The other 11/19 patients received anti-interleukin-17A and/or anti-interleukin-12/23 or anti-interleukin-23 (with/without anti-tumour necrosis factor-α/anti-interleukin-4/13), with stage-progression in 8 patients after a median of 8 months' treatment. Although, in general, biologics should be avoided in patients with MF, these results indicate that anti-tumour necrosis factor-α-monotherapy might not aggravate the disease course in early-stage patients. Interleukin-17A, interleukin-12/23 and interleukin-23 pathway-blockers may prompt progression of MF.

Vascular lesions in genital lichen sclerosus in pediatric patients.

BACKGROUND/OBJECTIVES: Lichen sclerosus is a rare, pruritic, mucocutaneous disease affecting mostly the anogenital area. Reports have occasionally associated lichen sclerosus with overlapping vascular lesions. This study explores this association in children. METHODS: A retrospective study was conducted in the dermatology unit of a pediatric tertiary care medical center. Electronic medical records were searched for patients diagnosed with lichen sclerosus from 2006 to 2019. Review of the cases was performed to identify overlapping vascular lesions and review the clinical course of overlap cases. RESULTS: Of 74 children diagnosed with lichen sclerosus during the study period, five (6.75%) had overlapping vascular lesions and genital lichen sclerosus. Four patients presented with reticular telangiectatic macules and patches (n = 4, 5.4%) that appeared at or shortly after disease onset; resolution occurred a few months after treatment initiation. The fifth patient presented with telangiectases that appeared more than 2 years after the onset of the first symptoms of lichen sclerosus (n = 1, 1.3%). CONCLUSION: Vascular lesions in children with genital lichen sclerosus are common and have variable clinical manifestations. Early appearance of reticular macules, patches, and papules is a variant of the disease and is followed by prompt resolution of these lesions. Pathogenesis is attributed to structural changes and repositioning of the papillary vascular plexus. These changes may be alarming to parents and therefore must be recognized by physicians to prevent unnecessary concern and investigations.

Idiopathic Papular Dermatitis in the Spectrum of Chronic Papular Eruptions (Subacute Prurigo): Reappraisal and Diagnostic Algorithm.

BACKGROUND: The clinical diagnosis of papular eruptions is common but poorly characterized in the literature and the etiology is often unknown. OBJECTIVE: To characterize the entity of idiopathic papular dermatitis in the spectrum of chronic papular eruptions. METHODS: The cohort consisted of patients who presented at a tertiary medical center in 2005-2014 with a papular eruption of at least 4 months' duration. Findings on histological analysis and thorough clinical investigation, performed in all cases, were collected. The patients completed a questionnaire on disease course and outcome. RESULTS: Sixty-five patients were included. Sixteen patients showed morphological changes over time and were excluded. Investigations in the remaining 49 patients with a consistent papular morphology yielded a well-defined diagnosis in 23 (46%). Twenty-six patients (54%; 14 male) were diagnosed with idiopathic papular dermatitis. Their mean age at onset was 61.6 ± 14.4 years and the mean duration of disease 3.11 ± 2.726 years. In 60%, the rash resolved with conservative treatment during follow-up (mean 4.35 ± 2.53 years). CONCLUSIONS: Chronic papular eruptions encompass a wide range of skin diseases. In more than half of the cases, the etiopathogenesis remains unclear. On the basis of our results, we propose a diagnostic algorithm for idiopathic papular dermatitis.

Heterozygous THBS2 pathogenic variant causes Ehlers-Danlos syndrome with prominent vascular features in humans and mice.

Ehlers-Danlos syndromes (EDS) are a group of connective tissue disorders caused by mutations in collagen and collagen-interacting genes. We delineate a novel form of EDS with vascular features through clinical and histopathological phenotyping and genetic studies of a three-generation pedigree, displaying an apparently autosomal dominant phenotype of joint hypermobility and frequent joint dislocations, atrophic scarring, prolonged bleeding time and age-related aortic dilatation and rupture. Coagulation tests as well as platelet counts and function were normal. Reticular dermis displayed highly disorganized collagen fibers and transmission electron microscopy (TEM) revealed abnormally shaped fibroblasts and endothelial cells, with high amount and irregular shape of extracellular matrix (ECM) substance, especially near blood vessels. Genetic analysis unraveled a heterozygous mutation in THBS2 (NM_003247.5:c.2686T>C, p.Cys896Arg). We generated CRISPR/Cas9 knock-in (KI) mice, bearing the heterozygous human mutation in the mouse ortholog. The KI mice demonstrated phenotypic traits correlating with those observed in the human subjects, as evidenced by morphologic, histologic, and TEM analyses, in conjunction with bleeding time assays. Our findings delineate a novel form of human EDS with classical-like elements combined with vascular features, caused by a heterozygous THBS2 missense mutation. We further demonstrate a similar phenotype in heterozygous THBS2Cys896Arg KI mice, in line with previous studies in Thbs2 homozygous null-mutant mice. Notably, THBS2 encodes Thrombospondin-2, a secreted homotrimeric matricellular protein that directly binds the ECM-shaping Matrix Metalloproteinase 2 (MMP2), mediating its clearance. THBS2 loss-of-function attenuates MMP2 clearance, enhancing MMP2-mediated proteoglycan cleavage, causing ECM abnormalities similar to those seen in the human and mouse disease we describe.

In Vivo Effects of Prostaglandin Analogues Application by Topical Drops or Retrobulbar Injections on the Orbital Fat of a Rat Model.

PURPOSE: To assess the in vivo effects of bimatoprost 0.03% (Lumigan®) on the orbital fat in a rat model. METHODS: Twenty rats were randomly divided into two groups: bimatoprost was administrated to the right eye by topical drops (group 1) or retrobulbar injection (group 2), and saline was administrated to the left eye by similar administration routes (controls). Four weeks later, all rats were sedated and euthanized, both orbits exenterated, and thin sections through the intraconal orbital fat were obtained. RESULTS: Average adipocyte cell count was significantly lower in the bimatoprost treated orbits (drops or retrobulbar injection, 29.5 vs. 67.5 cells per slide in the control globes, p=0.046). Fat cells were not detected in 9/20 (45%) bimatoprost treated orbits     . CONCLUSIONS: Orbits treated with bimatoprost by drops or retrobulbar injection demonstrated significant decrease in adipocytes cell count compared with controls. Bimatoprost could be an effective treatment for inactive thyroid eye disease.

Single probe light reflectance spectroscopy and parameter spectrum feature extraction in experimental skin cancer detection and classification.

Skin cancer, an anomalous development of skin cells in the epidermis, is among the most common types of cancer worldwide. Because of its clinical importance and to improve early diagnosis and patient management, there is an urgent need to develop noninvasive, accurate medical diagnostic tools. To this aim, light reflectance spectroscopy over the visible and near-infrared spectral range (400-1000 nm) based on a single-fiber six-around-one optical probe was applied to extract nine features used for diagnostics. These features include skewness, entropy, energy, kurtosis, scattering amplitude, and others, and are spread over each of four different spectral signatures, namely, light reflectance, absorbance, scattering profile approximation, and absorption/scattering ratio. Our preliminary studies focused on 11 adult patients with diagnoses of malignant melanoma (n = 4), basal cell carcinoma (n = 5), and squamous cell carcinoma (n = 2) in a variety of locations on the body. Measurements were taken first in vivo before surgery, at the site of the lesion and from healthy skin of the same patient, and ex vivo after surgical excision, where the lesion was rinsed in saline solution and measurements of the reflected light from the "inside" facing plane of the tissue were taken in the same manner. Overall, experimental results demonstrate that by examining a variety of wavebands, features, and statistical metrics, we can detect and distinguish cancer from normal tissue and different cancer subtypes. Nevertheless, discrepancies in results between in vivo and ex vivo tissue were observed and explanations for these discrepancies are discussed.

Real-life experience with chlormethine gel for early-stage mycosis fungoides with emphasis on types and management of cutaneous side-effects.

BACKGROUND: Real-life efficacy data on the recently approved once daily application of chlormethine gel (CG) for mycosis fungoides (MF) is limited, and detailed characterization of the side effects and their management are strikingly sparse. OBJECTIVE: To evaluate the efficacy and particularly the side effect profile of CG in early-stage MF patients in a real-life setting. METHODS: We performed a single-center retrospective analysis of 66 early-stage MF adult patients treated with CG in 2016-2019. RESULTS: Treatment with a once-daily application (52%), or at lower frequencies (48%), in some with topical corticosteroids (TCS) (40%), resulted in an overall response rate of 50%, with no significant difference between stage IA and IB. Cutaneous side effects (56%) included irritant or allergic contact dermatitis (36%, mostly mild/moderate and manageable by reducing application frequency and/or adding TCS or interrupting treatment), unmasking effect (9%), hyperpigmentation (14%), and pruritus (9%). Withdrawal due to side effects occurred in 19.6% of patients (15% for contact dermatitis). CONCLUSION: In real-life management, flexible regimens of CG sometimes with TCS, show efficacy in early-stage MF and may reduce the rate of contact dermatitis, the main treatment-limiting side effect. Practical recommendations with emphasis of the types, time of appearance, and management of side effects are provided.

Facial demodicosis in the immunosuppressed state: a retrospective case series from a tertiary referral center.

BACKGROUND: Data on Demodex in the immunosuppressed state is limited, focusing mainly on patients with human immunodeficiency virus and hematological malignancies. The aim of this study was to describe the manifestations of facial demodicosis in diverse immunosuppressive states. METHODS: The medical records of all patients followed at a Demodex outpatient clinic of a tertiary medical center from January 2008 to November 2020 were retrospectively reviewed. Data on patients who were immunosuppressed while with demodicosis were retrieved. RESULTS: The cohort included 28 patients (17 women and 11 men; median age, 58 years). Types of immunosuppression included treatments with hydroxyurea for polycythemia vera/essential thrombocytosis, mycophenolic acid, tacrolimus, and prednisone for liver and/or kidney transplantation, prednisone with cyclosporine/methotrexate/azathioprine/rituximab mainly for autoimmune diseases, mercaptopurine with/without anti-tumor necrosis factor alpha (TNF-α) for Crohn's disease, chemotherapy for neoplasms, anti-TNF-α for psoriasis, and Cushing's syndrome. The clinical types of demodicosis included: papulopustular, erythematotelangiectatic and fulminant rosacea, hyperpigmented, pityriasis folliculorum, pustular folliculitis, and dermatitis. The diverse clinical presentations led to various differential diagnoses. Topical treatment with ivermectin (monotherapy/combination with other treatments) was effective. CONCLUSION: Clinicians treating immunosuppressed patients should be familiar with the different forms of demodicosis and include them in the differential diagnosis of facial eruptions.

Clinical approach to skin eruptions induced by anti-TNF agents among patients with inflammatory bowel diseases: insights from a multidisciplinary IBD-DERMA clinic.

BACKGROUND AND AIMS: Skin eruptions are prevalent among patients with inflammatory bowel diseases (IBD), often associated with therapies and frequently leading to dermatological consults and treatment interruptions. We aimed to assess the impact of joint shared decision-making in a multidisciplinary (MDT) IBD-DERMA clinic. METHODS: This retrospective cohort study assessed a consecutive group of patients with IBD who were referred for consultation in an MDT clinic at a tertiary referral center in Israel. RESULTS: Over 1 year, 118 patients were evaluated in the MDT-IBD-DERMA clinic: 68 (57.6%) males; age - 35.2 ±â€„13.5 years, disease duration - 7.1 (interquartile range: 3.7-13.9) years; Crohn's disease - 94/118 (79.6%). Skin eruption induced by an anti-tumor necrosis factor (TNF) were the most common diagnoses [46/118 (39%)], including psoriasiform dermatitis (PD) - 31/46 (67.4%) and inflammatory alopecia (IA) - 15/46 (32.6%). Of these, 18 patients (39.1%) continued the anti-TNF agent concomitantly with a topical or systemic anti-inflammatory agent to control the eruption. The remaining 28 patients (60.9%) discontinued the anti-TNF, of whom 16/28 (57.1%) switched to ustekinumab. These strategies effectively treated the majority [38/46 (82.6%)] of patients. Continuation of the anti-TNF was possible in a significantly higher proportion of patients with PD: 12/31 (38.7%) than only one in the IA group, p = 0.035. There was a higher switch to ustekinumab among the IA 7/15 (46.6%) compared with the PD 7/31 (22.6%) group, P = .09. Following IBD-DERMA advised intervention, IBD deteriorated in 9/4 6(19.5%) patients, 5/9 on ustekinumab (PD versus IA, P = NS). CONCLUSION: Shared decision-making in an integrated IBD-DERMA clinic allowed successful control of skin eruptions while preserving control of the underlying IBD in more than 80% of cases. Patients with IA profited from a switch to ustekinumab.

Evaluation of the 13C-octanoate breath test as a surrogate marker of liver damage in animal models.

BACKGROUND: Octanoate (also known as sodium octanoate), a medium-chain fatty acid metabolized in the liver, is a potential substrate for non-invasive breath testing of hepatic mitochondrial beta-oxidation. METHODS: We evaluated the 13C-octanoate breath test (OBT) for assessing injury in acute hepatitis and two rat models of liver cirrhosis, first testing octanoate absorption (per os or intraperitoneally (i.p.)) in normal rats. We then induced acute hepatitis with thioacetamide (300 mg/kg/i.p., 24-h intervals). Liver injury end points were serum aminotransferase levels and 13C-OBT (24 and 48 h following initial injection). Thioacetamide (200 mg/kg/i.p., twice per week, 12 weeks) was used to induce liver cirrhosis. OBT and liver histological assessment were performed every 4 weeks. Bile duct ligation (BDL) was used to induce cholestatic liver injury. We completed breath tests with 13C-OBT and 13C-methacetin (MBID), liver biochemistry, and liver histology in BDL and sham-operated rats (baseline, 6, 14, 20 days post-BDL). RESULTS: Octanoate absorbs well by either route. Peak amplitudes and cumulative percentage dose recovered at 30 and 60 min (CPDR30/60), but not peak time, correlated with acute hepatitis. Fibrosis stage 3 at week 8 significantly correlated with each OBT parameter. Cholestatic liver injury (serum bilirubin, ALP, gamma-GT, liver histology) was associated with significant suppression of the maximal peak values and CPDR30/60, respectively (P<0.05),using MBID but not 13C-octanoate. CONCLUSIONS: OBT is sensitive for potentially evaluating liver function in rat models of acute hepatitis and thioacetamide-induced liver cirrhosis but not in cholestatic liver injury. The MBID test may be better for evaluation of cholestatic liver disease in this model.

Malignant melanoma clinically mimicking pyogenic granuloma: comparison of clinical evaluation and histopathology.

Amelanotic melanomas (AMMs) account for a small proportion of all melanomas. They pose a risk of delayed diagnosis and, consequently, poor prognosis. AMMs may atypically present as a pyogenic granuloma-like lesion. This study sought to investigate the prevalence and clinical and histological features of AMM masquerading as pyogenic granuloma. The database of a tertiary medical center was screened for all patients pathologically diagnosed with melanoma in 2005-2016. Those with a suspected primary (i.e. pre-excision) clinical diagnosis of pyogenic granuloma were identified, and their demographic, clinical, histologic, and outcome data were collected from the medical files. Of 2038 patients diagnosed with melanoma, 10 (∼0.5%) had a pyogenic granuloma-like AMM. The mean±SD age at lesion presentation was 56±18.9 years and the mean time from lesion appearance to diagnosis was 91.5±117.1 months. Nine tumors were located on the skin surface, and one on the oral mucosa. The mean lesion size was 19.6±14.1 mm and the mean Breslow's depth was 6.47±3.1 mm; all tumors presented in the vertical growth phase. Seven (70%) patients had lymph node involvement or metastasis at diagnosis. Two patients died of the disease within 1 year of diagnosis. Given the potential lethality of AMM and the benign nature of pyogenic granuloma, clinician recognition of pyogenic granuloma-like AMMs is crucial. In the presence of a pyogenic granuloma-like lesion, findings of older patient age and large tumor size should raise the index of suspicion and prompt a biopsy study, thereby ensuring early and accurate treatment.

A Unique Clinicopathological Manifestation of Fungal Infection: A Case Series of Deep Dermatophytosis in Immunosuppressed Patients.

BACKGROUND: Dermatophytes are the most common cause of superficial fungal infections in humans. Deep dermatophytosis, however, is rare, described to date only in isolated case reports, usually in the setting of systemic immunosuppression. OBJECTIVE: To present the 15-year experience of a tertiary dermato-mycology clinic with the diagnosis and treatment of deep dermatophytosis. METHODS: Patients were identified by database search. Clinical, mycological, histological, and treatment data were collected from the medical files. RESULTS: Ten patients were identified: nine after solid-organ transplantation and one undergoing chemotherapy, all diagnosed within 3 years after beginning immunosuppression (average 7.5 months). The infective agent in nine cases was Trichophyton rubrum. All patients presented with concurrent superficial fungal infections. Complete resolution was noted in response to systemic antifungal agents. There was no histological evidence of hair-follicle involvement. LIMITATIONS: The limitations of the study were the retrospective design and the small cohort size. CONCLUSION: This case-series study suggests that deep dermatophytosis is a separate entity, distinct from Majocchi's granuloma. It occurs only in immunocompromised patients and is characterized by discrete nodules, an indolent course, the absence of follicular invasion, and proximity to a superficial dermatophyte infection. Systemic antifungal treatment leads to complete resolution. The urgent need for the treatment of superficial fungal infections in immunocompromised patients is emphasized.

Widespread morbilliform rash due to sorafenib or vemurafenib treatment for advanced cancer; experience of a tertiary dermato-oncology clinic.

BACKGROUND: In the literature, there are minimal data for the treatment of grade 2 or 3 morbilliform/atypical target lesion rashes secondary to sorafenib or vemurafenib given for patients with advanced stage cancer. This poses a dilemma for clinicians, particularly in patients with advanced neoplastic disease for whom other optional treatments are limited. METHODS: The cohort included data on all patients attending the dermato-oncological clinic at a tertiary medical center that presented in 2011-2014 with a widespread rash following treatment with sorafenib or vemurafenib. All patients were prospectively followed. RESULTS: Eight patients met the study criteria. Five, under sorafenib, aged 50-65 years, presented with an extensive grade 2 (involving 20-30% of the body surface area, two patients) or grade 3 (three patients) morbilliform rash, 5-10 days after onset of the drug. Two had atypical target lesions. The dosage was temporarily reduced in only two patients, and oral steroids were added in four. Under vemurafenib, three patients presented with an extensive grade 3 morbilliform rash 5-10 days after onset of treatment. Two had atypical target lesions. The dose was temporarily reduced in one, and another patient stopped the drug at her own initiative; both also received steroids. The rash subsided after 2-3 weeks in all eight patients, allowing continuation of the treatment at the regular dose. CONCLUSION: Our cohort suggests that not all cases of widespread morbilliform rash or atypical erythema multiforme, which occur under treatment with sorafenib or vemurafenib, given for advanced cancer, require discontinuation of therapy.