DIFFERENTIAL DIAGNOSIS OF ANNULAR SKIN LESIONS - A CLINICAL REVIEW.

Annular lesions are a peculiar type of presentation of various skin disorders. The primary efflorescence can be either macule, papule, plaque, urticaria or vesicle. Depending on the primary efflorescence involved, the differential diagnoses can be delimited. It is important to identify secondary features such as scaling and discolorations. Additional symptoms may include pruritus, burning sensations or hypoesthesia. Depending on the clinical findings and medical history, confirmation of suspected working diagnosis is achieved by laboratory work-up, including histology and microbiology (mycology) studies.

Oral eosinophilic ulcer, an Epstein-Barr virus-associated CD30+ lymphoproliferation?

Eosinophilic ulcer of the oral mucosa is a benign lesion of unclear pathogenesis mostly affecting the tongue. It has been suggested to represent a reactive pattern to several stimuli. We report on a 12-year-old boy who presented with a painless infiltrating ulcer on the gingiva of the lower jaw, which was covered by necrotic yellowish slough. There were no pathologic features of the jawbones or regional lymph nodes. Histopathological, immunohistochemical and gene rearrangement studies were in agreement with eosinophilic ulcer with predominant oligoclonal CD3+ and CD30+ T lymphocytes expressing the Epstein-Barr virus membrane protein. The ulcer resolved within 4 weeks and follow-up for 3 years revealed no evidence of recurrence. Epstein-Barr virus may have played a role in triggering this reactive lymphoproliferative disorder.

Side-effects of topical androgenic and anabolic substances and steroids. A short review.

UNLABELLED: There is an increasing interest, including androgenic and anabolic substances (AAS). The uncritical use may be associated with severe adverse effects. We observed five patients with different patterns of adverse reaction to AAS: two females and three males, they were identified when seeking medical help and advice. The following adverse effects from of AAS have been observed: deepening of the voice due to topical use of AAS in an anti-cellulite cream; circumscribed hypertrichosis and late onset acneiform eruptions due to testosterone replacement therapy after ovariectomy; homolateral gynecomastia and infertility, acne and striae distensae in males using injectable AAS. CONCLUSIONS: ASS can trigger significant adverse effects. An interdisciplinary approach may be necessary for evaluation. The dermatologists should be familiar with the adverse effects.

Practical aspects of management of recurrent aphthous stomatitis.

Treatment of recurrent aphthous stomatitis (RAS) remains, to date, empirical and non-specific. The main goals of therapy are to minimize pain and functional disabilities as well as decrease inflammatory reactions and frequency of recurrences. Locally, symptomatically acting modalities are the standard treatment in simple cases of RAS. Examples include topical anaesthetics and analgesics, antiseptic and anti-phlogistic preparations, topical steroids as cream, paste or lotions, antacids like sucralfate, chemically stable tetracycline suspension, medicated toothpaste containing the enzymes amyloglucosidase and glucoseoxidase in addition to the well-known silver nitrate application. Dietary management supports the treatment. In more severe cases, topical therapies are again very useful in decreasing the healing time but fail to decrease the interval between attacks. Systemic immunomodulatory agents, like colchicine, pentoxifylline, prednisolone, dapsone, levamisol, thalidomide, azathioprine, methotrexate, cyclosporin A, interferon alpha and tumour necrosis factor (TNF) antagonists, are helpful in resistant cases of major RAS or aphthosis with systemic involvement.

Skin physiology and textiles - consideration of basic interactions.

The skin exerts a number of essential protective functions ensuring homeostasis of the whole body. In the present review barrier function of the skin, thermoregulation, antimicrobial defence and the skin-associated immune system are discussed. Barrier function is provided by the dynamic stratum corneum structure composed of lipids and corneocytes. The stratum corneum is a conditio sine qua non for terrestrial life. Impairment of barrier function can be due to injury and inflammatory skin diseases. Textiles, in particular clothing, interact with skin functions in a dynamic pattern. Mechanical properties like roughness of fabric surface are responsible for non-specific skin reactions like wool intolerance or keratosis follicularis. Thermoregulation, which is mediated by local blood flow and evaporation of sweat, is an important subject for textile-skin interactions. There are age-, gender- and activity-related differences in thermoregulation of skin that should be considered for the development of specifically designed fabrics. The skin is an important immune organ with non-specific and specific activities. Antimicrobial textiles may interfere with non-specific defence mechanisms like antimicrobial peptides of skin or the resident microflora. The use of antibacterial compounds like silver, copper or triclosan is a matter of debate despite their use for a very long period. Macromolecules with antimicrobial activity like chitosan that can be incorporated into textiles or inert material like carbon fibres or activated charcoal seem to be promising agents. Interaction of textiles with the specific immune system of skin is a rare event but may lead to allergic contact dermatitis. Electronic textiles and other smart textiles offer new areas of usage in health care and risk management but bear their own risks for allergies.

Non-sarcoidal, non-tuberculoid granuloma in common variable immunodeficiency.

Sarcoidal (non-caseating) or tuberculoid granulomas are cutaneous manifestations of common variable immunodeficiency (CVID). In this case report, we describe a patient with CVID but with non-sarcoidal, non-tuberculoid granuloma. The 29-year-old Egyptian male patient presented with a vitiliginous patch on the chin of 1 year duration and multiple recurrent warts on the hands and feet of 8 years duration. He is a known case of CVID with chronic diarrhea, recurrent otitis media, pneumonia, purulent conjunctivitis, septic arthritis, hepato-splenomegaly, and generalized lymphadenopathy. In addition, he had evidence of multiple non-tender subcutaneous nodules predominantly juxta-articular and recurrent rheumatoid-like arthritis. The skin overlying the nodules was either normal or slightly erythematous. Laboratory findings revealed markedly reduced serum immunoglobulins (IgG 3.4, n = 7.2-16.9 g/l; IgA 0.1, n = 0.69-3.82 g/l and IgM 0.1, n = 0.63-2.77 g/l) and deficient T cell function. Histopathologic examination of a skin nodule showed well demarcated areas of fibrinoid degeneration of collagen that stain homogeneously and are surrounded by histiocytes in a palisading arrangement, suggestive of granuloma annulare. No microorganisms could be detected. Serology for rheumatoid factor and HIV infection has been persistently negative. Although most infections, including common warts responded well to intravenous immunoglobulin replacement therapy (12 g/i.v., every 2 weeks) and oral broad spectrum antibiotic therapy, the subcutaneous nodules persisted. The vitiliginous patch responded favorably and disappeared within 24 local PUVA sessions. Since skin nodules are asymptomatic, no further treatment was given.

Endothelin-1 is significantly elevated in plasma of patients with vitiligo treated with psoralen plus ultraviolet A.

BACKGROUND: Recent evidence suggests that systemic psoralen plus ultraviolet A (PUVA) therapy may have a stimulatory effect on melanocytes, not only locally but also systemically. Aim. We aimed to assess endothelin-1 (ET-1), a potent melanocyte mitogen, in plasma of PUVA-treated paients with vitiligo. METHODS: ET-1 was sequentially assessed (using ELISA) in patients with nonsegmental vitiligo treated with PUVA (n = 20), at 8, 16 and 24 h following the PUVA session. Evaluations took place at 0, 1 and 3 months of therapy. Patients with psoriasis (n = 15) treated identically and healthy subjects not receiving any therapy (n = 15) served as controls. Vitiligo Area Scoring Index (VASI) and Psoriasis Area Severity Index (PASI) scores were simultaneously evaluated. RESULTS: ET-1 was significantly lower in vitiligo than in psoriasis at month 0 (8.2 +/- 3.6 vs. 13.7 +/- 5.4 pg/mL; P = 0.03) and it was significantly higher in both than in healthy controls at all time points of the PUVA sessions (P < 0.001). In vitiligo, it significantly increased at month 3 at 8 (8.2 +/- 3.6 vs. 10.8 +/- 2.7 pg/mL; P = 0.02) and 16 h (8.2 +/- 3.6 vs. 11.5 +/- 3.9 pg/mL; P < 0.01), whereas in psoriasis, it significantly decreased at month 3 at 8 (13.7 +/- 5.4 vs. 3.5 +/- 0.4 pg/mL; P < 0.01) and 16 h (13.7 +/- 5.4 vs. 6.3 +/- 4 pg/mL; P = 0.01). In contrast to psoriasis, sequential values of vitiligo revealed insignificant variance (P > 0.05). VASI score significantly decreased at month 3 (19 +/- 9.6 vs. 11.9 +/- 7.3; P < 0.01), whereas PASI score significantly decreased at months 1 (38.2 +/- 16.1 vs. 13.8 +/- 3; P < 0.05) and 3 (38.2 +/- 16.1 vs. 7 +/- 2.6; P = 0.03). There was a significant indirect correlation of ET-1 with VASI score (P < 0.01) and a significant direct correlation with PASI score (P < 0.01). CONCLUSION: Systemic PUVA therapy in vitiligo may have a generalized mitogenic effect on melanocytes through the release of ET-1 into the circulation.

Psoralen plus ultraviolet A irradiation-induced lentigines arising in vitiligo: involvement of vitiliginous and normal appearing skin.

Psoralen plus ultraviolet A irradiation (PUVA therapy) is commonly used for the management of vitiligo in which perifollicular repigmentation is the usual response pattern. However, excessive PUVA therapy may be associated with adverse effects. We report a case of generalized vitiligo that has been extensively treated with topical and systemic PUVA therapy for several years with the development of extensive and widespread stellate and irregularly shaped black and brown macules (lentigines). Interestingly, the lentigines were observed not only in the normally pigmented skin but also within the depigmented lesions that were lacking the perifollicular response pattern. The lesions developed in the exposed and unexposed skin areas. No evidence of skin malignancy was observed clinically and no melanocyte atypia was detected histopathologically. Cryotherapy may be used in the management of the lentigines; however, because of the extent of lesions this was impractical in our case.

Sildenafil citrate significantly improves nocturnal penile erections in sildenafil non-responding patients with psychogenic erectile dysfunction.

Effects of sildenafil citrate on nocturnal penile tumescence and rigidity (NPTR) were evaluated among sildenafil non-responding patients with psychogenic erectile dysfunction. All patients (n=30), equally divided into groups I and II, completed four consecutive nights using the RigiScan Plus device. Sildenafil citrate (50 mg) was given in the third night in group I and in the fourth in group II, whereas a placebo was given in the remaining nights. Additional patients (n=12) receiving only a placebo served as a control group. Results of NPTR recordings revealed neither significant differences between the control and non-sildenafil nights of both test groups, nor between the corresponding values of both groups (P>0.05). On the other hand, when sildenafil citrate nights of groups I and II taken together were compared with placebo nights, a significant increase of total events duration (P<0.001), average rigidity of the tip (P<0.05) and base (P<0.01), and rigidity activity unit (RAU) and tumescence activity unit (TAU) of tip and base (P<0.001) was observed. These results suggest that performance anxiety may be responsible for failure of response during awakening.

Mitogen requirements of normal epidermal human melanocytes in a serum and tumor promoter free medium.

Normal human melanocytes were cultivated in a serum free medium and the proliferation rate and antigen expression in the absence of each supplement was assessed every 3 days for 3 weeks. Results showed that the proliferation rate was significantly decreased in the absence of basic fibroblast growth factor, insulin and bovine pituitary extract as assessed 3 and 6 days of incubation (< 0.01). From day 9 through day 21, absence of transferrin, hydrocortisone, calcium, cholera toxin and epidermal growth factor was associated with a significant decrease of proliferation (< 0.001). Cells incubated with plain medium were almost absent from culture plates on day 6 and afterwards (< 0.0001). No evidence of contamination by epidermal and dermal cells was detected as all cultivated cells were labeled with MAbs HMB-45 and K.1.2.58. Absence of each supplement did not substantially affect antigen expression. It is concluded that basic fibroblast growth factor, insulin, and bovine pituitary extract are significant mitogens for melanocytes grown in a serum free medium from the very early phases of their growth.

Differential effects on melanocyte growth and melanization of low vs. high calcium keratinocyte-conditioned medium.

Epidermal keratinocytes secrete several growth factors that stimulate melanocyte proliferation and melanin pigment synthesis in vitro. As the epidermis is formed of two distinct layers, i.e. basal cell layer and suprabasal cell layers, and both are functionally and biologically different compartments, it was interesting to investigate which type of epidermal keratinocytes modulate melanocyte proliferation and function most. Normal human epidermal melanocytes (HMel) were incubated with melanocyte-conditioned medium (M-CM) and low Ca2+ and high Ca2+ keratinocyte-conditioned medium (K-CM) obtained from the same skin source of melanocytes. The morphology, proliferation rate and melanin synthesis were evaluated at days 3, 6 and 12 of incubation. The results showed no evidence of major morphological changes in the epidermal melanocytes with any of the conditioned media, although marked dendrite formation was observed in coculture of melanocytes and differentiated keratinocytes. On the other hand, low Ca2+ K-CM induced a mild but statistically significant stimulation of melanocyte growth in a time-dependent manner. The significant percentage increase was evident on day 6 (124.6%, P < 0.05) and on day 12 (138.1%, P < 0.01) of incubation. In contrast, high Ca2+ K-CM showed no significant effect on melanocyte proliferation (P > 0.05). Both low Ca2+ and high Ca2+ K-CM stimulated melanin synthesis, although synthesis induced by low Ca2+ K-CM was higher than that of high Ca2+ K-CM. The significant percentage increase induced by low Ca2+ K-CM was evident on day 6 (117.9%, P < 0.05) and on day 12 (127.8%, P < 0.05) of incubation, whereas it was evident with high Ca2+ K-CM only on day 12 (119.7%, P < 0.05) of incubation. It is concluded from the above data that keratinocytes grown at a low Ca2+ level release factors that stimulate melanocyte proliferation as well as melanin synthesis, whereas keratinocytes grown at a high Ca2+ level release factors that only stimulate melanin synthesis. This may provide an explanation of the anatomical position of melanocytes and may play a part in the pigmentary changes following injury to epidermal cells.

Oral psoralen with UV-A therapy releases circulating growth factor(s) that stimulates cell proliferation.

BACKGROUND: The mechanism by which oral psoralen with UV-A (PUVA) stimulates melanocyte proliferation in vitiligo is unknown. This study was conducted to examine the hypothesis that it does so by stimulating the release of growth factors that stimulate melanocyte proliferation. DESIGN: We examined the effect of serum samples obtained from patients with vitiligo before and following 2 and 4 months of PUVA therapy, and from non-PUVA-treated patients with vitiligo and normal individuals on the growth of melanocytes in vitro. SETTING: Outpatient clinic in referral center. PATIENTS: The study was conducted on serum samples obtained from 18 patients with vitiligo, 8 of whom were treated with PUVA, and from 10 normal individuals. INTERVENTION: Treatment with PUVA. MAIN OUTCOME MEASURE: Ability of serum samples to stimulate the growth of melanocytes in culture. RESULTS: Proliferation of melanocytes in serum collected after 4 months of PUVA therapy was on the average 3-fold greater than that in serum samples collected from the same patients prior to therapy with PUVA. This circulating growth factor was absent in serum samples of non-PUVA-treated patients with vitiligo and normal individuals. The effect was nonspecific, as it also stimulated the proliferation of fibroblasts. CONCLUSIONS: These findings suggest that PUVA treatment results in the release into the circulation of growth factor(s) that can stimulate a proliferation of melanocytes and of other cells. This could account for the repigmentation of vitiligo by PUVA treatment. As the growth factor(s) also stimulated the growth of other cells, it could also explain the thickening of the epidermis that occurs following exposure to UV light.

[Pre-myopathic versus amyopathic dermatomyositis. 2 personal cases and review of the literature]. / Präemyopathische versus amyopathische Dermatomyositis. Zwei eigene Beobachtungen und Literaturübersicht.

The so-called amyopathic dermatomyositis is a rare variant of dermatomyositis which has attracted increasing interest during the last years. One finds the classical signs of dermatomyositis such as periorbital edema and erythema, erythematous macular and papular lesions localized at bony prominences (so-called Gottron's papules), generalized pruritus, photosensitivity, and a cutaneous histopathologic picture compatible with skin lesions of dermatomyositis. Crucial for the diagnosis is the exclusion of myositis by clinical examination, EMG and histology. Furthermore, longterm supervision of patients is advisable in order not to miss the appearance of early signs of myositis. The longest reported follow-up of amyopathic dermatomyositis patient is 4 years; however, it cannot be excluded that these cases will eventually culminate in classical dermatomyositis. In this paper we describe two cases and discuss the differential diagnosis and therapy; also, the term "Premyopathic dermatomyositis" is proposed, to indicate that the full picture is to be expected in most cases.

Evidence for a complement-mediated inhibition and an antibody-dependent cellular cytotoxicity of dermal fibroblasts in alopecia areata.

Immunological mechanisms have long been suggested to mediate hair loss in alopecia areata. In this process hair bulb melanocytes and dermal papilla fibroblasts are believed to be primarily involved. In the present study we further investigated the role of humoral factors in alopecia areata. Three different experiments were performed on normal human epidermal melanocytes as well as normal human dermal fibroblasts: (i) incubation with medium containing 2, 10, or 20% alopecia areata serum (n = 12 patients) for 16 h, (ii) incubation with medium supplemented with preheated alopecia areata serum (1 h at 56 degrees C) and healthy human fresh serum as a complement source (1:1) and (iii) incubation with 2, 10 or 20% alopecia areata serum but, in addition, containing peripheral blood mononuclear cells from healthy subjects (effector/target ratio, 50:1). As controls, normal human fibroblasts and normal human epidermal melanocyte cultures were also incubated with serum from healthy individuals (n = 5) under the same culture conditions. The results showed that alopecia areata serum exerted a significant stimulation of proliferation of both normal human fibroblasts (p > 0.05 at 2%, p > 0.05 at 10%, p < 0.05 at 20%), and normal human epidermal melanocytes (p > 0.05 at 2%, p < 0.05 at 10%, p > 0.05 at 20%).(ABSTRACT TRUNCATED AT 250 WORDS)

Further evidence for involvement of both cell mediated and humoral immunity in generalized vitiligo.

Immunohistochemical and immunoserological evidence supports the involvement of both cell-mediated and humoral mechanisms in the pathogenesis of melanocyte destruction in vitiligo. Punch biopsies from depigmented vitiliginous skin (VS), normal-looking pigmented skin (PS), and marginal skin (MS) from patients with generalized vitiligo (n = 15) were labeled with K 1.2.58, OKM1 (CD11b), Leu 11b (CD16), Leu 19 (CD56), IFN-gamma receptor, IL-2 receptor (CD25), IgG, IgM, C3c, and C3d MoAbs. In addition, in vitro effects of vitiligo sera (n = 13) on human newborn melanocytes (HMel) under different culture conditions were studied. The immunohistochemical findings showed absence of K 1.2.58+ epidermal melanocytes in VS and abnormal morphology in MS. In these areas, a few CD11b+ cells in the dermis and epidermis could be detected but no significant numbers of CD16+ or CD56+ cells were seen among the mononuclear cellular infiltrate. IL-2 and IFN-gamma receptors were clearly expressed by the cellular infiltrate. No significant deposition of complement or immunoglobulin was seen. The addition of vitiligo sera to HMel cultures induced a significant cellular proliferation. The stimulation of cell proliferation occurred regardless whether the sera were added alone or when preheated (56 degrees C for 1 hr) and then supplemented with a complement source (P < 0.01 at 2%, P < 0.001 at 10%, and P < 0.01 at 20% for sera alone) (P > 0.05 at 2%, P < 0.05 at 10%, and P < 0.01 at 20% for decomplemented sera plus complement).(ABSTRACT TRUNCATED AT 250 WORDS)

Aquagenic pruritus as a presenting symptom of polycythemia vera.

A female patient was presented because of a prickling sensation that appeared shortly after warm water contact. Examination revealed no abnormality, but water exposure was followed by pruritus without any visible skin changes. Blood and bone marrow examinations revealed abnormalities typical of polycythemia vera. Skin biopsy before and after warm water challenge showed increased numbers of mononuclear cells in the papillary dermis and epidermis particularly after water exposure. Phlebotomy was associated with prompt cessation of pruritus.

Nonsegmental vitiligo: decrease of the CD45RA+ T-cell subset and evidence for peripheral T-cell activation.

Peripheral T-lymphocytes from 16 randomly selected patients with nonsegmental vitiligo were labeled with monoclonal antibodies recognizing T-cell receptor (TCR) alpha/beta, TCR gamma/delta, CD3, CD4, CD8, CD45RA, CD45RO, CD11b, CD11c, CD16, CD56, CD25, CD54, and HLA-DR antigens. In comparison with matched controls, a significant decrease of the CD45RA+ subset (P less than 0.03) together with significant increase of the circulating HLA-DR+ cells (P less than 0.02) was found. No other alterations were detected. These findings may point to some autoimmune phenomena involved in the pathogenesis of the disease. The increased HLA-DR expression indicates the presence of activated peripheral T-cells. Thus, our data provide new and further evidence for T-cell dysregulation in nonsegmental vitiligo.