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.

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.

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.

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.

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.

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.

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 genital warts: facts and controversies.

There are two opposing approaches in the treatment of genital warts: (1) the traditional approach advocates complete elimination of all lesions, and (2) a second approach regards condyloma as merely a cosmetic nuisance. After a long journey through many arguments and scientific papers, we have concluded that many unknowns, uncertainties, and controversies concerning the value of treatment of genital warts in terms of clearing and curing the disease (ie, eradicating the viruses, preventing cancer, and reducing infectivity). There is no consensus at present of whether treatment of men with evidence of genital human papillomavirus infection influences the natural history of their female sex partner's cervical disease.

New insights in the immunologic basis of psoriasis.

Psoriasis vulgaris is a multifactorial heritable disease characterized by severe inflammation resulting in poorly differentiated, hyperproliferative keratinocytes. Recent advances in genetic analyses have implicated components regulating the interleukin (IL)-23 and nuclear factor-kappaB pathways as risk factors for psoriasis. These inflammatory pathways exhibit increased activity in skin lesions, and promote secretion of various cytokines, such as IL-17 and IL-22. Unrestrained, the activated inflammatory cytokine network in psoriasis may trigger a vicious cycle of inflammation and cellular proliferation that ultimately results in lesion formation. These advances in genetic analyses, together with the progress made in targeted biological therapy, pave the path to tailor treatment on the basis of an individual's genetic and immunologic profile.

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.

Neutrophilic dermatosis of the hands after influenza vaccination.

An otherwise healthy 72-year-old man presented with a painful eruption composed of grouped hemorrhagic purulent blisters on erythematous plaques, on both palms of his hands, which appeared 12 h after he had been vaccinated against influenza. Based on the patient's history, physical examination, histopathological and laboratory findings, the diagnosis of neutrophilic dermatosis of the hands (NDH) was made. NDH is currently considered a distributional variant of Sweet's syndrome (SS). It is identical to atypical pyoderma gangrenosum (PG) and pustular vasculitis of the hands. There are only seven reported cases of SS after vaccination, none of them with lesions confined solely to the palms or soles. Our current case is the third one of SS following influenza vaccination.

Eruptive acral lentigines--a new paraneoplastic sign?

Cutaneous signs may be the first indications of an internal disease. Any definitive sign of a neoplastic disease is of special importance since early diagnosis and early treatment may make a telling difference in improving prognosis. Presented is a 68-year-old patient with advanced stage melanoma that was associated with the appearance of multiple acral lentigines. The exact time-course of onset of the lentigines in relation to the formation of the melanoma could not be established. However, from the information we could take out of our patient, it is clear that the lentigines had appeared either shortly before or after the appearance of the melanoma. In conclusion we suggest that the present case represents a new paraneoplastic sign.

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.