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.

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.

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.

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.

Retinoid receptors.

"Retinoid" refers to the naturally occurring compounds with vitamin A activity and to synthetic analogues of retinol. Retinoids are key regulators of differentiation, proliferation, and inflammation. Their successful use in the treatment of various skin diseases and neoplasias has revolutionized the practice of dermatology as well as oncology. This article focuses on the retinoid receptors to elucidate our understanding of their complex biologic activity that is reflected in their therapeutic clinical effects as well as in their adverse reactions.

Acute generalized exanthematous pustulosis following a spider bite: report of 3 cases.

Acute generalized exanthematous pustulosis (AGEP) is a rare severe cutaneous adverse reaction caused mostly by drugs. Three of 22 AGEP cases (13.6%), recruited by us as part of two prospective multinational studies, occurred 24 to 48 hours after a spider bite. We suggest that a spider bite is a possible trigger for AGEP.

Rare syndromes.

Dermatologists may also encounter patients presenting with skin lesions that reflect an underlying endocrine disorder not commonly seen in daily practice. Some of these endocrine disorders include glucagonoma, neurofibromatosis type 1, McCune-Albright syndrome, multiple endocrine neoplasia, the Carney complex, carcinoid tumors, and mastocytosis. The clinical syndrome classically associated with glucagonoma includes necrolytic migratory erythema, weight loss, diabetes mellitus, anemia, cheilitis, venous thrombosis, and neuropsychiatric symptoms. The hallmarks of neurofibromatosis type 1 are the multiple café-au-lait spots and associated cutaneous neurofibromas. Other presenting features include freckling, peripheral neurofibromas, Lisch nodules, bone abnormalities, tumors, neurologic abnormalities and hypertension. McCune-Albright syndrome is characterized by café-au-lait spots, polyostotic fibrous dysplasia, sexual precocity, and hyperfunction of multiple endocrine glands. Multiple endocrine neoplasia type 2A is characterized by medullary thyroid cancer, pheochromocytoma, and primary parathyroid hyperplasia. In some patients with multiple endocrine neoplasia type 2A, cutaneous lichen amyloidosis may also be present. Multiple endocrine neoplasia type 2B is characterized by medullary thyroid cancer and pheochromocytoma but not hyperparathyroidism. The syndrome also includes mucosal neuromas, typically involving the lips and tongue, intestinal ganglioneuromas and a marfanoid habitus. Multiple endocrine neoplasia type 1 is an autosomal dominant predisposition to tumors of the parathyroid glands (four-gland hyperplasia), anterior pituitary, and pancreatic islet cells; hence, the mnemonic device of the "3 Ps"; multiple cutaneous lesions (angiofibromas and collagenomas) are frequent in patients with multiple endocrine neoplasia type 1. Carney complex may be viewed as a form of multiple endocrine neoplasia because affected patients often have tumors of two or more endocrine glands, including primary pigmented nodular adrenocortical disease (some with Cushing's syndrome), pituitary adenoma, testicular neoplasms, thyroid adenoma or carcinoma, and ovarian cysts. Additional unusual manifestations include psammomatous melanotic schwannoma, breast ductal adenoma, and a rare bone tumor, osteochondromyxoma. Carcinoid syndrome is the term applied to a constellation of symptoms mediated by various humoral factors elaborated by some carcinoid tumors; the major manifestations are diarrhea, flushing, bronchospasm, and cardiac valvular lesions. Mast cell diseases include all disorders of mast cell proliferation. These diseases can be limited to the skin, referred to as "cutaneous mastocytosis," or involve extracutaneous tissues, called "systemic mastocytosis." Patients present with urticaria pigmentosa, mastocytoma, or diffuse cutaneous mastocytosis. Systemic involvement may be gastronintestinal, hematologic, neurologic, and skeletal.

[Acute generalized exanthematous pustulosis (AGEP) following intake of furosemide].

INTRODUCTION: Acute generalized exanthematous pustulosis (AGEP) is an acute pustular eruption with unique clinical features, a rapid clinical course and a typical histopathology. The causative agents are mostly drugs but other triggers have also been described. CASE REPORT: A 52 year-old woman with a history of diabetes mellitus type II, dyslipidemia and osteomyelitis was treated for about a year with metformin (Glucophage) and simvastatin (Simovil) tablets. Due to the osteomyelitis, the patient was started on a regimen of intravenous vancomycin as well as furosemide tablets (Fusid) for pedal edema. About seventeen days after beginning treatment with vancomycin and a week after starting furosemide the patient was hospitalized due to an acute pruritic pustular eruption, involving most of her body surface area. Both vancomycin and furosemide treatment were discontinued, and topical treatment was provided. The clinical course was rapid with spontaneous resolution of the pustules followed by a characteristic pin-point post-pustular desquamation. The morphological, clinical and histological findings suggested a definite case of AGEP based on the EuroSCAR scoring system. The latent period between the initiation of medication intake and the appearance of AGEP, as well as a literature search, suggest that furosemide might be the incriminated drug. CONCLUSION: We have described a rare case of typical AGEP most probably induced by furosemide.

The challenge of drug-rechallenge: Facts and controversies.

The accurate identification of the culprit drug inducing a patient's cutaneous adverse drug reaction is important to avoid future adverse reactions and to provide safe alternative drugs. The assessment has to rely on the clinical signs, the time course, and response to treatment. Sometimes, additional diagnostic procedures are also needed. If diagnostic procedures such as in vivo skin testing and in vitro laboratory tests do not lead to conclusive results, confirmation of a presumptive diagnosis by a rechallenge test is often the only reliable way to establish a diagnosis. This procedure should be undertaken only with great caution and a compelling need, because a rechallenge test might cause severe or even fatal reactions. Contraindications and ethical considerations should be taken into account and an individual risk-benefit calculation must be performed in every case.

The role of diet in acne: facts and controversies.

Acne is the most prevalent skin condition. It has a substantial effect on the quality of life of teenagers worldwide. Among acne patients from different societies and cultures, diet is uniformly regarded as a major cause in the pathogenesis of acne. We reviewed the up-to-date literature regarding acne and culprit foods such as dairy products, chocolate, and fatty foods. Unfortunately, after reviewing the existing data, there are no answers but there are definitely more questions, because there is no clear proof about whether these issues are facts or misconceptions.

Psoriasis and systemic inflammatory diseases: potential mechanistic links between skin disease and co-morbid conditions.

Psoriasis is now classified as an immune-mediated inflammatory disease (IMID) of the skin. It is being recognized that patients with various IMIDs, including psoriasis, are at higher risk of developing "systemic" co-morbidities, e.g., cardiovascular disease (CVD), metabolic syndrome, and overt diabetes. In non-psoriatic individuals, the pathophysiology of obesity, aberrant adipocyte metabolism, diabetes, and CVDs involves immune-mediated or inflammatory pathways. IMIDs may impact these co-morbid conditions through shared genetic risks, common environmental factors, or common inflammatory pathways that are co-expressed in IMIDs and target organs. Given that pathogenic immune pathways in psoriasis are now well worked out and a large number of inflammatory mediators have been identified in skin lesions, in this review we will consider possible mechanistic links between skin inflammation and increased risks of (1) obesity or metabolic alterations and (2) CVD. In particular, we will discuss how well-established risk factors for CVD can originate from inflammation in other tissues.

Comparison of the dynamics and correlates of transmission of Herpes Simplex Virus-1 (HSV-1) and Varicella-Zoster Virus (VZV) in a sample of the Israeli population.

Herpes simplex virus types-1 (HSV-1) and Varicella-zoster virus (VZV) are herpes viruses that share many characteristics. However, HSV-1 spreads by close contact while VZV spreads mainly by the airborne route. In this study we compared the dynamics and correlates of transmission of these viruses in the same population. In 2000-2001, 1555 sera from an age-stratified general population sample were tested using commercial ELISA kits to measure type-specific HSV-1 and varicella IgG antibodies. The VZV seroprevalence increased rapidly with age reaching 50% seropositivity by the age of 3 years, while HSV-1 reached 50% seropositivity at the age of 14 years. The highest VZV force of infection was in the 3.5-5.5-year age group followed by the 5.5-10.5 years age group, while for HSV-1 the age specific force of infection was substantially lower and stable over the various age groups. Multivariate analysis revealed that HSV-1 seroprevalence was significantly, independently associated with age, country of birth, country of origin, ethnicity, socio-economic status and VZV sero-status. Only age, country of origin and HSV-1 sero-status were found to be associated with VZV seropositivity. In developed countries such as Israel the transmission of VZV is much quicker and less dependent on socioeconomic status as compared with HSV-1.

Seroprevalence of herpes simplex virus 1 and 2 and correlates of infection in Israel.

BACKGROUND: The prevalence of infections with herpes viruses 1 and 2 (HSV1 and HSV2) have significantly changed in the developed countries during the last three decades. This study provides up-to-date estimates of HSV-1 and HSV-2 seroprevalence and information on the correlates of infection in a representative sample of the Israeli population. METHODS: Three thousand eight hundred and eighty-one sera collected in 2000-2001 from an age-stratified general population sample were tested using an indirect IgG ELISA for type-specific HSV-1 and HSV-2 antibodies. RESULTS: Unadjusted HSV-1 seroprevalence was 59.8% (95% confidence interval: 58.2-61.4) and increased with age in both genders. Multivariate analysis revealed that HSV-1 seroprevalence rates were significantly higher in females, non-Jews, subjects who were not born in Israel, inhabitants of Jerusalem and Southern Israel and among subjects also seropositive for HSV-2. Unadjusted HSV-2 seroprevalence among adults was 9.2% (95% confidence interval: 7.9-10.2), and was higher in females, peaking at 20.5% in females aged 40-49. In a multivariate model, females, subjects who were not born in Israel and residents of Jerusalem and Southern Israel were significantly associated with HSV-2 seropositivity. CONCLUSIONS: HSV-1 seroepidemiology in Israel resembles the trends in industrialized countries. HSV-2 seroprevalence rates is in the lower range reported across Europe.

Decline in the prevalence of antibodies to herpes simplex virus types 1 and 2 among Israeli young adults between 1984 and 2002.

OBJECTIVE: The objective of this study was to estimate the seroprevalence of herpes simplex virus (HSV) types 1 and 2 in male and female soldiers discharged from the Israel Defense Force (IDF) over a period of 18 years. GOAL: The goal of this study was to study the secular trends of HSV-1 and HSV-2 infection rates in Israeli young adults. STUDY DESIGN: Three consecutive cross-sectional studies were carried out on stored sera of systematic random samples of soldiers (median age = 20.8) discharged from the IDF in 1984-1985, 1992-1993, and 2001-2002. HSV-1 and -2 seroprevalence was analyzed using indirect IgG enzyme-linked immunosorbent assay for type-specific antibodies. RESULTS: There was a significant decrease in HSV-1 and HSV-2 seropositivity rates at discharge from the army and an estimated 10-fold decline in the incidence rates of HSV-2 infection during the military service over the last 2 decades. CONCLUSIONS: The decline in HSV-1 seroprevalence rate is similar to that reported from other industrialized countries. The decrease in HSV-2 seroprevalence and transmission rates among Israeli young adults is steeper than that reported from Western countries.