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.

Mammalian target of rapamycin inhibitors for prolonged secondary prevention of nonmelanoma skin cancer in solid organ transplant recipients.

Immunosuppressive agents are essential for graft survival in solid-organ transplant recipients (SOTRs), but they have substantial durable side effects, including a higher incidence of aggressive nonmelanoma skin cancers (NMSCs). Hitherto, only one class of immunosuppressants, mammalian target of rapamycin inhibitors (mTORi), may inhibit skin tumor formation, however their durable effectiveness is controversial. To evaluate the sustained effectiveness of mTORi in reducing NMSCs' incidence in SOTRs, a retrospective study was conducted in a specialized dermatology clinic for SOTRs of a tertiary university-affiliated medical center. SOTRs with a history of at least one histologically proven NMSC were followed for 6 years: 3 years after transplantation, before initiation of mTORi, and 3 years under mTORi treatment. The cohort consisted of 44 SOTRs. Treatment with mTORi was initiated on average 6.27 (3.34-6.34) years following transplantation. In the 3 years before mTORi treatment initiation, the mean number of new NMSCs per patient was 2.11 (1-14). This value decreased to 1.2 (0-19) in the 3 years under mTORi treatment (p = 0.0007). Analysis by NMSC type yielded a significant decrease in both SCCs and BCCs. This study found that mTORi are effective for prolonged secondary prevention of NMSCs in SOTRs.

Low-Dose Acitretin for Secondary Prevention of Keratinocyte Carcinomas in Solid-Organ Transplant Recipients.

BACKGROUND: Keratinocyte carcinomas, particularly squamous cell carcinoma (SCC), occur more frequently and aggressively in solid-organ transplant recipients (SOTRs) than in the general population. Systemic retinoids are effective in secondary prevention of keratinocyte carcinomas in this population, but their use is limited by adverse effects including a rebound effect in cases of treatment discontinuation. OBJECTIVE: Our aim was to determine whether low-dose acitretin is efficient in the secondary prevention of keratinocyte carcinomas in SOTRs. METHODS: This retrospective case-crossover study was conducted at a specialized dermatology clinic for SOTRs in a large transplantation center in 2010-2017. Patients with at least 1 previous keratinocyte carcinoma who were treated with acitretin 10 mg/day for 2 years were included. The main outcome was the difference in the number of new keratinocyte carcinomas diagnosed during treatment compared to during the 2-year pretreatment period. RESULTS: The cohort included 34 SOTRs. A significant reduction in the mean number of new keratinocyte carcinomas during treatment relative to the pretreatment period was observed (1.7 vs. 3.6, -53% p = 0.002). Similar results were noted on analysis by tumor type, for both SCC and basal cell carcinoma. CONCLUSION: This study of SOTRs demonstrated positive results for low-dose acitretin as a chemoprevention of keratinocyte carcinomas in this population.

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.

Prophylactic Topical Treatment for EGFR Inhibitor-Induced Papulopustular Rash: A Randomized Clinical Trial.

BACKGROUND: The incidence of epidermal growth factor receptor inhibitor (EGFRI)-induced papulopustular rash is 60-85%. OBJECTIVE: To investigate prophylactic topical treatment for EGFRI-induced rash. METHODS: A single-center, randomized, double-blind, placebo-controlled trial. Adult cancer patients initiating treatment with EGFRIs were randomized to receive facial topical treatment with chloramphenicol 3% + prednisolone 0.5% (CHL-PRED) ointment, chloramphenicol 3% (CHL) ointment, or aqua cream (AQUA). The primary end points were the incidence of ≥grade 3 rash using the Common Terminology Criteria for Adverse Events (CTCAE), on days 14 and 30. A subanalysis was conducted for incidence of a protocol-specified significant rash, defined as ≥10 facial papulopustular lesions. RESULTS: The per-protocol analysis on day 14 included 69 patients, who received CHL-PRED (21), CHL (23), or AQUA (25). The incidence of CTCAE ≥grade 3 rash was not statistically significant between arms; however, the incidence of the protocol-specified significant rash was: CHL-PRED 14%, CHL 39%, and AQUA 48% (p = 0.03, CHL-PRED vs. AQUA). At 30 days, the CTCAE ≥grade 3 incidence was similar, but the incidences of protocol-specified significant rash were 6%, 16%, and 43% (p = 0.03, CHL-PRED vs. AQUA). No significant differences were found between CHL and CHL-PRED and between CHL and AQUA. CONCLUSIONS: Prophylactic topical CHL-PRED was efficacious when compared to AQUA, in the treatment of EGFRI-induced facial papulopustular rash.

Trends in Kaposi's Sarcoma Morbidity: A Retrospective Cohort Study of Heart and Lung Transplant Recipients.

Data on post-transplant Kaposi's sarcoma in heart and lung transplant recipients are sparse. This study examined the incidence of biopsy-proven post-transplant Kaposi's sarcoma in thoracic organ recipients over a period of 20 years. As mammalian target of rapamycin inhibitors were introduced in 2006 as optional maintenance immunosuppressive therapy, the overall results were analysed and stratified into 2 groups: 1996 to 2005 and 2006 to 2016. A total of 867 transplant recipients met the study criteria. Post-transplant Kaposi's sarcoma was diagnosed in 7 (0.81%) patients. Five cases (0.19% of transplant recipients) were recorded in 1996 to 2005 and 2 (0.03% of transplant recipients) in 2006 to 2016 (p = 0.04). Multivariable logistic regression analyses identified the following as risk factors: period of transplantation (odds ratio (OR) 4.844, 95% confidence interval (95% CI) 1.156-20.291), age at transplantation (OR 1.066, 95% CI 0.992-1.145), and North African origin (OR 7.282, 95% CI 12.55-42.254). This study found a decreased incidence of post-transplant Kaposi's sarcoma over the last 20 years, mainly attributed.

Evaluation of multiplex real-time PCR for identifying dermatophytes in clinical samples-A multicentre study.

The gold-standard method for dermatophyte identification involves direct microscopy and culture, which have inherent shortcomings. Only few molecular methods have been standardised for routine clinical work. This study aimed to develop and test a platform for identifying the most common dermatophytes in Israel using multiplex real-time polymerase chain reaction (RT-PCR). Specific primers were designed for the multiplex system (LightCycler 480) according to known cultures and validated by reference isolates. The dermatophyte detection rate was compared to smear and culture in 223 clinical samples obtained from a tertiary medical centre. Inconsistencies between methods were evaluated by sequencing. The RT-PCR was further evaluated in 200 community-based samples obtained from a health maintenance organisation and 103 military-personnel-based samples analysed at a central laboratory. In hospital-based clinical samples, complete concordance between methods was observed in 190 samples (85%; Kappa = 0.69). In most cases of non-concordance, sequencing was consistent with RT-PCR results. RT-PCR correctly identified all smear- and culture-positive cases in community and military-personnel samples. The results were available within 4 hours. The multiplex RT-PCR platform is a rapid and efficient method for identifying dermatophyte species in clinical samples and may serve as a first step in the diagnostic algorithm of superficial fungal infections.

Juvenile mycosis fungoides: cutaneous T-cell lymphoma with frequent follicular involvement.

BACKGROUND: The literature on mycosis fungoides (MF) in children/adolescents is sparse. OBJECTIVE: We sought to evaluate the characteristics of juvenile MF in a large cohort. METHODS: Data were collected on all patients with MF, aged 18 years or younger at the time of clinicopathologic diagnosis, who attended the Rabin Medical Center Dermatology Department, Petach Tikva, Israel, between 1994 and 2012 and were followed up prospectively. RESULTS: There were 50 patients (30 male; mean age 11.4 years at diagnosis); 18 (36%) had Fitzpatrick skin type IV or higher. All were given a diagnosis of early-stage disease (IA-IIA) except 1 (tumor stage, IIB). Eight had classic MF lesions only and 42 had other variants, alone or in combination; these were mainly hypopigmented MF (n = 29) and cases with subtle but clear clinicopathologic features of folliculotropic MF (FMF) (n = 18). Among the various skin-targeted therapies, psoralen plus ultraviolet A (systemic/bath) proved beneficial for FMF. During a follow-up period of 0.25 to 15 years (mean 4.5), 2 patients progressed from stage IA to IB or IIA. LIMITATIONS: Relatively short follow-up is a limitation. CONCLUSIONS: This case series shows that FMF is not uncommon in children and adolescents. It is characterized by more superficial clinical features and less heavy perifollicular lymphocytic infiltrates than adult FMF, and responds well to psoralen plus ultraviolet A. The prognosis of childhood FMF remains unclear.

"Sunlight is said to be the best of disinfectants"*: the efficacy of sun exposure for reducing fungal contamination in used clothes.

BACKGROUND: Tinea pedis is a common chronic skin disease; the role of contaminated clothes as a possible source of infection or re-infection has not been fully understood. The ability of ultraviolet light to inactivate microorganisms has long been known and UV is used in many applications. OBJECTIVES: To evaluate the effectivity of sun exposure in reducing fungal contamination in used clothes. METHODS: Fifty-two contaminated socks proven by fungal culture from patients with tinea pedis were studied. The samples were divided into two groups: group A underwent sun exposure for 3 consecutive days and group B remained indoors. At the end of each day fungal cultures of the samples were performed. RESULTS: Overall, there was an increase in the percentage of negative cultures with time. The change was significantly higher in socks that were left in the sun (chi-square for linear trend = 37.449, P < 0.0001). CONCLUSIONS: Sun exposure of contaminated clothes was effective in lowering the contamination rate. This finding enhances the current trends of energy saving and environmental protection, which recommend low temperature laundry.

Treatment of tinea capitis - griseofulvin versus fluconazole - a comparative study.

OBJECTIVE: To compare the efficacy and safety of fluconazole and griseofulvin in the treatment of tinea capitis. PATIENTS AND METHODS: Patients with tinea capitis (n = 113) with positive fungal cultures entered the study. The patients were divided into four groups with different treatment regimes. Two groups received griseofulvin 15 or 25 mg/kg/day and two groups received fluconazole 4 or 6 mg/kg/day, all for up to 12 weeks. RESULTS: Griseofulvin was found to be slightly better than fluconazole. The lower doses for both griseofulvin and fluconazole required significantly longer treatment duration until mycological cure than the higher doses, independent of the fungus type. CONCLUSIONS: Since no significant difference was found between the drugs, it is suggested that the choice should be based on tolerability, availability and cost of the drugs.

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.

Onychomycosis in psoriatic patients - rationalization of systemic treatment.

Nail changes in patients with psoriasis have been reported with varying prevalence. Onychomycosis has been reported in up to 47% of the psoriasis patients. The purpose of this study was to determine the prevalence of nail abnormalities, onychomycosis in psoriasis and response to itraconazole treatment. We evaluated 312 patients suffering from psoriasis for nail changes and onychomycosis. Patients having laboratory confirmation of onychomycosis were treated with three courses of itraconazole (400 mg day(-1) for 1 week). Of 312 patients with psoriasis, 67 (21.5%) patients had nail changes, 23 (34%) of them suffered from onychomycosis. Complete cure (clinical and mycological) was achieved in 30% of the patients with onychomycosis. The response to treatment of onychomycosis with itraconazole in psoriasis patients was found to be lower than in the general population. Considering the low response to onychomycosis systemic therapy in psoriatic patients and the potential side-effects of the treatment, the rationality of this treatment is questionable.

Differing effect of systemic anti psoriasis therapies on platelet physiology--a case report and review of literature.

BACKGROUND: Psoriasis is a common, chronic relapsing inflammatory skin disease. Lately, there is increasing evidence that psoriasis is more than "skin deep". Epidemiological studies showed that severe psoriasis might have also important systemic manifestations such as metabolic deregulations, cardiovascular disease (CVD) and increased mortality. Moreover, recently psoriasis patients were found to have platelet hyperactivity. CASE PRESENTATION: This is a case report and review of the literature. We present a patient with long standing severe psoriasis vulgaris with marked thrombocytosis. His thrombocytosis did not correlate with disease severity but rather with the different treatments that he was exposed to, subsiding only during treatment with anti Tumor Necrosis Factor (TNF)- agents. A literature review revealed that in rheumatoid arthritis, another systemic inflammatory disease; interleukin (IL)-6 might be implicated in causing thrombocytosis. CONCLUSION: This unique case report illustrates that different systemic treatments for psoriasis might have implications beyond the care of skin lesions. This insight is especially important in psoriasis patients in view of their deranged hemostatic balance toward a prothrombotic state, which might increase the risk of thrombosis and CVD. Therefore, further studies analyzing the effect of different drugs on platelets physiology are warranted.

Phacomatosis pigmentopigmentalis: aberrant Mongolian spots and segmental café au lait macules.

We report a case of an otherwise healthy male newborn, with segmental café au lait spots on his left buttocks and left thigh down to the medial knee, in a nevoid pattern, and an aberrant Mongolian spot on the ipsilateral cheek of the buttocks in a checkerboard pattern. We propose the name phacomatosis pigmentopigmentalis in analogy to phacomatosis pigmentovascularis, and phacomatosis pigmentokeratotica.

Acute generalized exanthematous pustulosis and psoriasis: what can be learned from comorbidities.

BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) is a rare pustular severe cutaneous adverse reaction. Differentiating between AGEP and pustular psoriasis may represent a diagnostic challenge. We sought to evaluate the prevalence of comorbidities in a series of patients with AGEP compared to a series of patients with psoriasis vulgaris and to a series of patients with drug-related psoriasis. METHODS: Medical records of 14 patients with AGEP, 33 patients with psoriasis vulgaris, and 18 patients with drug-related psoriasis were reviewed. The presence of comorbidities was recorded, and a comparative analysis was performed. RESULTS: A personal history of psoriasis was present in 4 (28%) patients with AGEP compared to 12 (66%) patients with drug-related psoriasis (Pv=0.03). The prevalence of psoriasis-related morbidities was significantly lower in the AGEP group compared to the psoriasis group and to the drug-related psoriasis group (Pv<0.01, 0.05, respectively). Each of the psoriasis-related morbidities had significantly lower prevalence in the AGEP group compared to the psoriasis group and to the drug-related psoriasis group (Pv<0.01). CONCLUSIONS: In conclusion, differences between AGEP, psoriasis vulgaris, and drug-related psoriasis regarding the prevalence of psoriasis-related morbidities may assist differentiation in borderline cases.

Stevens-Johnson syndrome and toxic epidermal necrolysis induced by amifostine during head and neck radiotherapy.

Amifostine is an organic thiophosphate prodrug used for cytoprotection against toxic effects of radiotherapy and chemotherapy. In a European prospective study of SJS/TEN, six patients were suspected to have SJS/TEN associated with amifostine. Our findings suggest that the risk of life-threatening cutaneous adverse reactions to amifostine could be significantly increased.

Cutaneous manifestations of pituitary gland diseases.

The pituitary gland is also known as the "master" gland of the endocrine system, because it controls the functions of the other endocrine glands. From its lofty position in the sella turcica it sends signals to the thyroid gland, adrenal glands, ovaries and testes. It modulates the production of a variety of hormones that have dramatic effect on metabolism, blood pressure, sexuality, reproduction, growth, milk production and other vital body functions and therefore are essential for homeostasis. Since changes of the internal environment often mirrors in the skin, this article will focus on the skin changes in pituitary gland diseases. Disorders resulting from excessive secretion of hormones as well as from hormones deficiency of this complex endocrine organ will be reviewed.

Accidental BTX drops into the conjunctival sac: is this a cause for concern?

Any injector can accidentally spill a few drops of BTX into the eye. It might very well be a harrowing experience to the uninformed: the good news is that the patient is at no risk of untoward sequelae. Although the BTX that diffuses into the orbit from these injections might well cause adverse effects, the same neurotoxin dropped into the eye is no more than a matter of wasting expensive material. We present herein our experience with such an accident, and support it with theoretical considerations.

Profile of acute generalized exanthematous pustulosis in Israel during 2002-2005: results of the RegiSCAR Study.

BACKGROUND: Acute generalized exanthematous pustulosis is a rare pustular severe cutaneous adverse reaction characterized by a rapid clinical course and unique histological findings. It is usually attributed to drugs, although other factors have also been implicated. OBJECTIVES: To analyze demographic, clinical and laboratory data of AGEP cases in Israel, based on the RegisCAR study, a multinational European study. METHODS: Patients included in the present study were actively recruited by the Israeli RegiSCAR network, which comprised 10 dermatology departments and units. The cases were validated by a multinational expert committee of dermatologists based on a standardized scoring system. RESULTS: Overall, 11 potential cases of AGEP were collected in Israel: 9 (81.8%) definite and 2 (19.2%) possible. The adjusted annual incidence of AGEP in Israel was 0.35/million/year. The nine definite cases that entered the analyses showed a male/female ratio of 0.28 with an age range of 10-60 years. Most cases were reported during the summer months. The clinical course and laboratory findings in most of our patients were in accordance with previous reports. A drug etiology was suspected in the majority of cases and consisted of analgesics (66.7%), antibiotics (22.2%) and non-steroidal anti-inflammatory drugs (11.1%) as the main culprit drugs. CONCLUSIONS: Whereas the clinical and laboratory findings of AGEP in Israel corresponded to the reported features of AGEP in the literature, some unique findings were noted, namely, marked female predominance, seasonality and a profile of culprit drugs.