Yonit Wohl

Environmental Risk Factors for Mycosis Fungoides

The rising incidence rates of mycosis fungoides (MF) call for an explanation. Thus, environmental and lifestyle factors were speculated to play a role in the development of lymphoproliferative diseases. It is thought that continuous activation of skin T helper lymphocytes leads to malignant transformation of a specific clone. Possible risk factors that have been implicated are occupational chemical exposure, radiation, drugs and infections. The carcinogenic process is probably multifactorial and multistep, combining the genetic predisposition of the individual and his immune status with various exogenous factors. Using advanced and accurate exposure assessment tools, recent epidemiological data indicate that occupational exposure to chemicals, primarily to aromatic halogenated hydrocarbons, is a major risk factor to develop MF in men (odds ratio 4.6), while exposure to pesticides, a subgroup of the aromatic halogenated hydrocarbons, is a risk factor in both genders (odds ratio 6.8 for men and 2.4 for women). Apparently, concomitant infection with Staphylococcus aureus or with Borrelia species and chronic exposure to UVR are minor risk factors for the development of MF. Further assessment of occupational and environmental exposures is essential for the evaluation of their contribution to the etiology of MF. This will allow the application of preventive and surveillance measures along with adjustment of existing health policies.

A mixed immunoblistering disorder exhibiting features of bullous pemphigoid and pemphigus foliaceus associated with Spirulina algae intake

An 82‐year‐old healthy woman presented with bullae, partly hemorrhagic, on the trunk and extremities ( Fig. 1 ), secreting erosions, and submammary macerations ( Fig. 2 ). The blistering disease developed over a 2‐year period, during which she reported taking no drugs. She did, however, begin using a food supplement containing the blue–green alga Spirulina platensis 1 year before the onset of the eruption.

Normal levels and function of endothelial progenitor cells in patients with psoriatic arthritis

Endothelial progenitor cells (EPCs) are a population of bone marrow derived cells which have been attributed with the ability to migrate into areas of tissue ischemia and to posses reparative qualities. EPCs have been shown to be decreased in level and function in various inflammatory disorders. Psoriasis and psoriatic arthritis are associated with an increase in cardiovascular morbidity. The aim of the study was to investigate the number of EPCs among patients suffering from psoriasis and psoriatic arthritis. Patients suffering from active psoriasis and psoriatic arthritis were recruited as well as healthy controls. Disease activity was assessed with the DAS-28, BASDAI and PASI scores. Peripheral blood mononuclear cells were isolated and EPC numbers evaluated by FACS analysis using the CD34/133 and CD34/KDR. No significant difference was found between numbers of EPCs between healthy controls, patients with psoriasis and psoriatic arthritis. A significant correlation was found between levels of VGEF and the BASDAI score. The results of the current study do not support a significant role for EPCs in the pathogenesis of psoriasis and psoriatic arthritis.

Acetaminophen-induced lichenoid keratosis : a new way to look at an old lesion

Editor Acetaminophen (paracetamol) is a widely used analgesicantipyretic drug, easily obtained over the counter and generally well tolerated. Its potential for drug interactions is often underestimated. Adverse skin reactions, some life threatening, involve almost all arms of the innate and acquired immune systems, and include urticarial anaphylactoid reactions, fixed drug eruptions, pigmented purpuras, acute generalized exanthematous pustulosis, toxic epidermal necrolysis, and even a case of IgA bullous dermatosis. The association of acetaminophen with lichenoid eruption is rare. We encountered a case of what appeared to be acetaminophen-induced lichenoid keratosis (LK) in a 63year-old, otherwise healthy Ashkenazi Jewish woman who presented with a 2-week history of an asymptomatic, solitary, flat-topped, small ovoid plaque on the ventral side of the right arm. The plaque was erythematous, with a brownish hue. She had ingested acetaminophen for a headache 1 day prior to appearance of the lesion. She reported a previous episode of clinically diagnosed lichenoid eruption in the same area following ingestion of acetominophen, which disappeared and reoccurred after challenge, leaving no pigmentary changes. The lag time between ingestion of the drug and appearance of the lesions at that time was much longer than in the current incident. Histological examination of a completely excised lesion revealed a lichenoid inflammatory infiltrate obscuring the dermo-epidermal junction, with vacuolar changes, occasional Civatte bodies and pigment incontinence. The inflammatory infiltrate consisted mainly of T cell lymphocytes, with mixed CD4 and CD8 populations (fig. 1), but no eosinophils or plasma cells. The epidermis showed focal acanthosis without hypergranulosis or parakeratosis. Hyperpigmentation features of solar lentigo were encountered. In vitro interferon gamma release test performed on the patient’s lymphocytes, described previously, showed a rise in interferon release, with acetaminophen over the predrug test level (480 pg/mL vs. 350 pg/mL, respectively). This test is recognized as a safe, informative tool for identifying drugs associated with various forms of adverse cutaneous drug reactions. Table 1 summarizes the major clinical and histological features of LP-associated lesions, showing the overlap between entities. Our case exhibited LK clinically, with mixed histological evidence of LK and lichenoid drug eruption, suggesting that the two are in fact reactive immunological processes, probably to the same insult. This observation was supported by the positive rechallenge to acetaminophen, accompanied by the in vitro rise in the release of interferon gamma, a key orchestrating cytokine in T-lymphocyte processes. In view of the usual slow growth of lichenoid lesions, their appearance the third time only 1 day after ingestion of acetominophen is intriguing. This might be explained by the fact that in reactive recurrent cases like ours, local T cells are already activated, rendering a shortened lag time. fig. 1 Lichenoid inflammatory infiltrate obscuring the dermal epidermal junction with occasional Civatte bodies. Immunohistochemical stains of the lymphocyte infiltrate show pronounced CD4 (× 20).

Redness, a possible signpost for malignant melanoma.

To the Editor An observation of malignant melanoma patients who had a particular reddish appearance, mainly on the face, that could not be attributed to any medical cause including photosensitivity was first described by Brenner and Wolf1 and Tamir and Brenner.2 We have examined the mechanism and the significance of this observation in 14 patients who had been diagnosed and treated for melanoma in our clinic during 2002 and had been in follow-up for 8–12 months. Clinical data on the patients (Table 1) were compared to those of two other groups: 30 healthy individuals, and a cohort of patients with keratinocyte-derived tumours; 10 with squamous cell carcinoma (SCC), 10 with Bowen’s disease and 15 with basal cell carcinoma (BCC). Eight of the 14 (57%) melanoma patients exhibited a particular reddish appearance adjacent to and in the general vicinity of the primary tumour, consisting of an erythematous rash that had no distinguishable borders and was fairly confluent with the surrounding tissue. The rash occupied a large area near the malignant lesion: for example, melanoma of the upper back was accompanied by an erythematous rash covering most of the upper and middle back; melanoma of the lip was accompanied by an erythematous rash on the face and neck. None the six other melanoma patients and none of the subjects in the other two groups exhibited such a rash. During 8–12 months of follow-up, during which only patient 4 left the study, the rash remained unchanged in patients 2, 3 and 6, increased in extent and strength in patients 1 and 7, and diminished in extent and strength in patients 5 and 8. None of the melanoma patients who had no rash at the beginning of the study, and none of the subjects in the two control groups, developed a rash during the follow-up period. Melanoma cells can express growth factors and cytokines, having an autocrine and/or paracrine effect that permits autonomous growth of cells including tumour cells, endothelial cells, keratinocytes, fibroblasts, monocytes, lymphocytes and granulocytes,3 causing tumour development and metastasis. Other escape mechanisms of melanoma cells are self-tolerance to melanoma antigens, downregulation of class II major histocompatibility complex molecules, and the expression of FasL and HLA-G molecules by melanoma cells.4 Among the cytokines and growth factors produced by the melanoma cells are vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor-β2 (TGFβ2), and interleukin-10 (IL-10).3,4 VEGF, bFGF and TGF-β2 have a pro-angiogenic effect,5–7 while IL-10 may have an antiangiogenic effect.8 VEGF expression in primary and cutaneous metastatic melanoma was found to have an unfavourable effect on the prognosis of melanoma, and IL-10, TGF-β2, bFGF and VEGF plasma levels were increased in metastatic melanoma. The inverse plasma levels between IL-10 and VEGF in patients with metastatic melanoma may be attributed to their opposite effect on angiogenesis.4 This theory is supported by Doppler flowmetry measurements of higher superficial skin

The normal and abnormal breast

Heres a helpful review of what goes right and what can go wrong in the female and male breast, with emphasis on dermatologic and developmental disorders. New issues are demanding the clinicians attention, including the cosmetic effects of nipple piercing and tattooing.