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.

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.

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.

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.

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.

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.

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.

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.

"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.

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.

The effect of domestic laundry processes on fungal contamination of socks.

Tinea pedis is a common chronic skin disease. The role of contaminated clothes as a possible source of reinfection is not fully understood. This study was conducted to evaluate the efficacy of domestic laundering at different temperatures in the eradication of fungal pathogens from contaminated socks. Samples from 81 socks worn by patients suffering from tinea pedis underwent domestic laundering at either 40 °C or 60 °C. The socks were dried at room temperature; fungal cultures were taken from two samples from, respectively, the toe and heel areas of the socks. Samples from socks washed at 40 °C revealed 29 (36%) positive fungal cultures, of which 14 came from the toe and 15 from the heel areas of socks. Trichophyton rubrum was isolated in four specimens, and Aspergillus spp. were found in 20 (70%) specimens. Samples from the same socks washed at 60 °C revealed five (6%) positive fungal cultures, of which three came from the toe and two from the heel areas of socks. Only Aspergillus spp. were detected. Yeasts were eradicated at 40 °C. Contravening current trends for energy saving and environmental protection, laundering at low temperatures is not effective in eradicating fungal pathogens, which requires high-temperature laundering at 60 °C.

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.

Onychomycosis: a simpler in-office technique for sampling specimens.

BACKGROUND: In onychomycosis, proper specimen collection is essential for an accurate diagnosis and initiation of appropriate therapy. Several techniques and locations have been suggested for specimen collection. OBJECTIVE: To investigate the optimal technique of fungal sampling in onychomycosis. METHODS: We reexamined 106 patients with distal and lateral subungual onychomycosis (DLSO) of the toenails. (The diagnosis had previously been confirmed by a laboratory mycological examination­both potassium hydroxide [KOH] test and fungal culture­of samples obtained by the proximal sampling approach.) We collected fungal specimens from the distal nail bed first, and later from the distal underside of the nail plate. The collected specimens underwent laboratory mycological examination. RESULTS: KOH testing was positive in 84 (79.2%) specimens from the distal nail bed and only in 60 (56.6%) from the distal underside of the nail plate (P=.0007); cultures were positive in 93 (87.7%) and 76 (71.7%) specimens, respectively (P=.0063). Combining results from both locations showed positive KOH test results in 92 (86.8%) of the 106 patients and positive cultures in 100 (94.3%) patients. CONCLUSIONS: Based on our study, we suggest that in cases of suspected DLSO, material should be obtained by scraping nail material from the distal underside of the nail and then collecting all the material from the distal part of the nail bed.

Evaluation of SCORTEN on a cohort of patients with Stevens-Johnson syndrome and toxic epidermal necrolysis included in the RegiSCAR study.

The purpose of this study was to evaluate the severity-of-illness score called SCORTEN with respect to its predictive ability and by using data obtained in the RegiSCAR study, the most comprehensive European registry of patients with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). For advanced comparisons, an auxiliary score (AS) was defined using data obtained in a previous study. Three hundred sixty-nine patients with SJS/TEN were included in RegiSCAR between 2003 and 2005. The data needed for calculation of SCORTEN were available for 45% of patients. The score revealed a moderate predictive ability with a slight underestimation of the total number of in-hospital deaths by 11%, an area under the receiver operating characteristic curve of 0.75, and a Brier score of 0.14. Problems could be seen by analyzing subgroups such as patients with TEN. The AS was better calibrated but discriminated worse (area under the receiver operating characteristic curve: 0.72; Brier score: 0.14). With the help of a refined score derived from SCORTEN and AS, potential for a possible improvement could be demonstrated. The authors were able to show that the predictive ability of SCORTEN is acceptable. Although improvement might be possible, SCORTEN remains the tool of choice, whereas AS might be an alternative in retrospective settings with missing laboratory data.

Intertriginous lymphomatoid drug eruption.

A 76-year-old man developed a maculopapular purpuric eruption confined to the intertriginous areas (i.e. the inguinal, gluteal, and axillary folds). Two days before the eruption appeared, he had received a second course of chemotherapy consisting of cisplatinum 40 mg and gemcitabine (Gemzar) 1700 mg for the treatment of squamous cell carcinoma of the lung stage III B. The histologic picture was of either lymphomatoid drug eruption or lymphomatoid papulosis. The antineoplastic therapy was changed to once-weekly intravenous vinorelbine (Navelbine) 50 mg, a Vinca alkaloid, and the eruption resolved completely within two weeks without any further therapy. These circumstantial evidences support the diagnosis of intertriginous drug eruption. Our case is interesting and unusual in that it demonstrated a rare clinical presentation of drug eruption, namely, intertriginous drug eruption or baboon syndrome, with a histologic picture of a lymphomatoid drug eruption that can mimic lymphoma. We are unaware of any earlier reported case of baboon syndrome with a histologic picture of lymphomatoid drug eruption. The pathomechanisms of both types of drug eruption, i.e. baboon syndrome and lymphomatoid drug eruption, are not fully understood.

Treatment of scabies and pediculosis: facts and controversies.

Unlike many other skin diseases, success or failure of therapy of ectoparasitic infestation depends much more on how to use the topical preparation and whom we treat than on which scabicide or pediculicides to use. The diagnosis of scabies should no longer rely on the rather uncommon and unpractical sign of finding a burrow or the number of parasites per infected patient. Most infested individuals have been shown to have several-fold more acari than the oft-quoted average of 12 adult acari per infected patient that appears in most of our textbooks (stemming from Mellanby's work). Contrary to what Mellanby taught us, we know that indirect transmission (ie, without personal contact) does occur. As to which agent to use, the winner remains undeclared at present. Although indirect contact transmission of hair lice has been clarified after thousands of years of infestation, there are still numerous questions, uncertainties, disagreements, and controversies on the subject; for example, we know that lice survive immersion in water but are probably not transmitted in swimming pools. There is no consensus on the best or most correct way to diagnose lice, nor is the problem of resistance resolved. We do not recommend a "no-nit" policy.