Acquired Acrodermatitis Enteropathica Syndrome in a Kidney Transplant Receipt: A Case Report.

Acrodermatitis enteropathica syndrome (AE) is a clinical entity that results in severe zinc deficiency. It can be genetic or acquired. Acquired AE has been reported in patients with chronic liver disease, malabsorption syndrome, sickle cell anemia, and chronic renal failure. We present a kidney transplant recipient with skin rash and watery diarrhea. The patient had low serum zinc levels, which quickly resolved after zinc supplementation. Skin biopsy showed cytoplasmic pallor and vacuolization and ballooning degeneration of keratinocytes within the superficial epidermis, which may have led to confluent necrosis of keratinocytes. Large amounts of keratinosome-derived lamellae were found in the intercellular spaces in the keratinized area, probably related to disturbance of keratinosome metabolism due to zinc deficiency.

Terbinafine hydrochloride loaded liposome film formulation for treatment of onychomycosis: in vitro and in vivo evaluation.

Onychomycosis is a fungal infection of nail unit that is caused by dermatophytes. Oral Terbinafine hydrochloride (TBF-HCl) is being used for the treatment of onychomycosis since 24 years. The side effects caused by the systemic application and limitations of topical administration of this drug regarding the diffusion through nail lead to the development of a new formulation based on, TBF-HCl-loaded liposome. The newly obtained film formulations were prepared and characterized via several parameters, such as physical appearance, drug content, thickness, bioadhesive properties and tensile strength. In vitro and ex vivo permeation studies were performed to select an optimum film formulation for antifungal activity to show the efficiency of formulations regarding the treatment of onychomycosis. The in vitro release percentages of drug were found 71.6 ± 3.28, 54.4 ± 4.26, 56.1 ± 7.48 and 46.0 ± 2.43 for liposome loaded pullulan films (LI-P, LII-P) and liposome loaded Eudragit films (LI-E, LII-E), respectively. The accumulated drug in the nail plates were found 31.16 ± 4.22, 24.81 ± 5.35, 8.17 ± 1.81 and 8.92 ± 3.37 for LI-P, LII-P, LI-E and LII-E, respectively, which within therapeutic range for all film formulations. The accumulated drug in the nail plate was found within therapeutic range for all film formulations. The efficacy of the selected TBF-HCl-loaded liposome film formulation was compared with TBF-HCl-loaded liposome, ethosome, liposome poloxamer gel and ethosome chitosan gel formulations. It was found that TBF-HCl-loaded liposome film formulation had better antifungal activity on fungal nails which make this liposome film formulation promising for ungual therapy of fungal nail infection.

Treatment of onychomycosis using the 1 064 nm Nd:YAG laser: a clinical pilot study.

BACKGROUND: Nd:YAG lasers could be a safe and effective treatment modality for onychomycosis, without the side effects of drugs. Long and short-pulsed Nd:YAG lasers were used in this clinical study in a side-comparison manner without removal of onychomycotic nail material before treatment. PATIENTS AND METHODS: Big toenails of 10 patients were treated twice in a side-comparison manner with the short-pulsed Nd:YAG laser. Fungal cultures were taken and a histological examination was performed before treatment and after 9 months. Two independent investigators rated clearance using the "Onychomycosis Severity Index (OSI)" and standardized photographs at 3-month intervals. RESULTS: OSI-Scores decreased for 3.8 (15 %; p = 0.006), 4.8 (19 %; p = 0.0002) and 2.9 points (12 %; p = 0.04) within 3, 6 and 9 months. The positive culture rate at 9 months was significantly reduced to 35 % (p = 0.0003). Classification of severity of onychomycosis showed no change. The difference between the treatment regimens was not significant. CONCLUSIONS: These results suggest that treatment of onychomycosis with the Nd:YAG laser without removing mycotic nail material can lead to a temporary clinical improvement, a reduction of positive fungal cultures and an improvement of the Onychomycosis Severity Index. The treatment regimen should be optimized to be used as an effective antimycotic monotherapy.

Comparison of clobetasol propionate cream plus coal tar vs. topical psoralen and solar ultraviolet A therapy in palmoplantar psoriasis.

AIM: Palmoplantar psoriasis (PPP) produces significant morbidity and requires prompt treatment. Topical agents form the mainstay of therapy. We compared the efficacy and side-effect profile of a steroid/coal-tar combination with topical psoralen and solar ultraviolet A (PUVAsol) in PPP. METHODS: In total, 52 patients with PPP were randomized to receive either a combination of clobetasol propionate cream and coal tar daily (group 1) or topical PUVAsol on alternate days (group 2) for 16 weeks. Response was assessed as change in Psoriasis Activity and Severity Index (PASI) and Patient Global Assessment (PGA). RESULTS: Of the 52 patients, 43 completed the treatment phase. There was a reduction in PASI for the palms and soles in both treatment groups throughout the treatment period until week 16. There was a greater reduction in PASI in palmar psoriasis with topical PUVAsol, and a greater reduction in psoriasis of the soles with the steroid/coal-tar combination. In both groups, patients perceived 'good improvement'. Improvement or cure in palmar lesions was observed in 90% of cases in the topical steroid/coal-tar group and in 75% of cases in the topical PUVAsol group; for the soles, these figures were 76% and 79%, respectively. No adverse effects were experienced with the steroid/coal-tar combination, whereas for the topical PUVAsol, phototoxicity occurred in 22% of cases. CONCLUSION: Both treatments had comparable efficacy. In both groups, patients experienced 'good improvement' after 16 weeks of therapy.

Newer trends in the management of psoriasis at difficult to treat locations: scalp, palmoplantar disease and nails.

Psoriasis is a common, chronic, inflammatory disease with a wide range of clinical presentations. The disease severity ranges from mild to severe. Plaque type of psoriasis is the most common. A number of factors like previous treatment history and comorbid conditions influence the treatment of psoriasis in an individual patient. Location of the lesions is also an important consideration. Psoriasis localized to certain areas of the body like scalp, nails, palms and soles remains difficult to treat. These sites have been referred to as the difficult locations in literature. This article covers the management of psoriasis limited to these special areas.

Hypertension and hand-foot skin reactions related to VEGFR2 genotype and improved clinical outcome following bevacizumab and sorafenib.

BACKGROUND: Hypertension (HT) and hand-foot skin reactions (HFSR) may be related to the activity of bevacizumab and sorafenib. We hypothesized that these toxicities would correspond to favorable outcome in these drugs, that HT and HFSR would coincide, and that VEGFR2 genotypic variation would be related to toxicity and clinical outcomes. METHODS: Toxicities (> or = grade 2 HT or HFSR), progression-free survival (PFS), and overall survival (OS) following treatment initiation were evaluated. Toxicity incidence and VEGFR2 H472Q and V297I status were compared to clinical outcomes. RESULTS: Individuals experiencing HT had longer PFS following bevacizumab therapy than those without this toxicity in trials utilizing bevacizumab in patients with prostate cancer (31.5 vs 14.9 months, n = 60, P = 0.0009), and bevacizumab and sorafenib in patients with solid tumors (11.9 vs. 3.7 months, n = 27, P = 0.052). HT was also linked to a > 5-fold OS benefit after sorafenib and bevacizumab cotherapy (5.7 versus 29.0 months, P = 0.0068). HFSR was a marker for prolonged PFS during sorafenib therapy (6.1 versus 3.7 months respectively, n = 113, P = 0.0003). HT was a risk factor for HFSR in patients treated with bevacizumab and/or sorafenib (OR(95%CI) = 3.2(1.5-6.8), P = 0.0024). Carriers of variant alleles at VEGFR2 H472Q experienced greater risk of developing HT (OR(95%CI) = 2.3(1.2 - 4.6), n = 170, P = 0.0154) and HFSR (OR(95%CI) = 2.7(1.3 - 5.6), n = 170, P = 0.0136). CONCLUSIONS: This study suggests that HT and HFSR may be markers for favorable clinical outcome, HT development may be a marker for HFSR, and VEGFR2 alleles may be related to the development of toxicities during therapy with bevacizumab and/or sorafenib.

Evaluation of zinc level in skin of patients with necrolytic acral erythema.

BACKGROUND: Necrolytic acral erythema (NAE) is considered a cutaneous sign of hepatitis C virus infection. Its exact pathogenesis is still not fully understood, with some reports about decreased serum zinc levels but none about its level in the skin. OBJECTIVES: To assess skin (lesional and perilesional) and serum zinc levels in patients with NAE and compare them with levels in control subjects. METHODS: Fifteen patients with NAE and 10 healthy controls were included in this study. Assessment of zinc level, in serum by graphite furnace atomic absorption spectrophotometry and in lesional and perilesional skin biopsies by flame atomic absorption spectrometry, was done in all subjects. Re-evaluation of serum and lesional skin zinc level was done after oral zinc treatment. RESULTS: Mean±SD zinc levels were significantly lower in patients (serum 0·44 ± 0·13 mg L(-1) ; lesional skin 42·6 ± 18·9 mg L(-1) ; perilesional skin 32·5 ± 17·2 mg L(-1) ) than controls (serum 1·17 ± 0·29 mg L(-1) ; skin 100·1 ± 2·77 mg L(-1) ), with a positive correlation between lesional and perilesional skin zinc (r = 0·91, P < 0·01). Oral zinc supplementation significantly increased serum and skin zinc levels (by 159% and 4%, respectively; P < 0·05). CONCLUSIONS: NAE is associated with decreased serum and skin zinc levels. Oral zinc supplementation corrects decreased levels of plasma and skin zinc much earlier than the desired clinical benefits appear.

Paring and intense pulsed light versus paring alone for recalcitrant hand and foot warts: a randomized clinical trial with blinded outcome evaluation.

BACKGROUND AND OBJECTIVES: Treatment of recalcitrant viral warts remains a therapeutic challenge. Intense pulsed light (IPL) has been suggested effective to clear wart tissue. The objective was in a randomized controlled trial to assess the efficacy of paring followed by IPL versus paring alone for recalcitrant hand and foot warts. MATERIALS AND METHODS: Eighty-nine patients with recalcitrant hand and foot warts were included and randomized (1:1) to three treatments at 3-week intervals with either paring of warts followed by IPL or paring of warts alone. IPL was given with the Ellipse Flex IPL system (Danish Dermatologic Development A/S, Hørsholm, Denmark, 400-950 nm, 5.5 millisecond pulse duration in double pulses with a 2 millisecond interval, 26.0-32.5 J/cm(2) repetitive passes). The primary outcome was complete and partial clearance of warts evaluated by blinded photo assessment at 6 weeks after final treatment. Secondary outcomes were treatment related pain and adverse reactions. RESULTS: We found no significant difference in clearance of warts between the two intervention groups (OR 1.64, 95% confidence interval 0.62-4.38). Paring followed by IPL resulted in complete or partial clearance of wart tissue in nine (22%) and five patients (12.2%) versus five (13.5%) and four patients (10.8%) from paring alone. Mostly plantar warts were treated (92.1%). The pain intensity after paring and IPL was moderate and significantly higher than the pain intensity after paring alone (P<0.0005). No adverse reactions were observed from the two interventions. CONCLUSION: Paring followed by IPL did not differ significantly from paring alone in clearance of recalcitrant hand and foot warts but caused significantly more pain.

Fungal chitin-glucan scaffold for managing diabetic xerosis of the feet in menopausal women.

BACKGROUND: Corneocyte accumulation (hyperkeratosis, xerosis) commonly occurs in the stratum corneum (SC) of the feet of diabetic patients, as well as menopausal women. OBJECTIVE: To compare the effects of a 2.5% chitin-glucan formulation with its placebo, and commercially available glycerol formulations. METHODS: This two-step controlled double-blind, randomized, intra-individual study was performed in 30 type 1 and 2 diabetic menopausal women suffering from xerosis of the feet. The formulations were applied once daily for 3 weeks. Electrometric assessments were performed on three sites of the feet at entry in the study, at weekly intervals during the treatment phase, and in a 2-week follow-up out of treatment. Positive controls consisted in two commercially available formulations enriched in glycerol. RESULTS: Data revealed an unequivocal benefit provided by the 2.5% chitin-glucan formulation compared with placebo. The electrometric values were significantly higher at each evaluation time during both treatment and follow-up phases. The two glycerol-enriched formulations showed slightly different kinetics of SC moisturization. A steep increase was followed by a plateau level and a rapid decline after stopping the treatments. CONCLUSION: The increased moisturization of the SC of the sole probably improves the desquamation process and reduces xerosis of the soles.

Efficacy of topical PUVA soaks for palmoplantar dermatoses: an audit.

BACKGROUND: With a lack of evidence base for individual topical PUVA protocols, treatment is presently based on the consensus of current practice. This audit was designed to investigate the effectiveness of topical PUVA for palmoplantar dermatoses. METHODS: Phototherapy notes were reviewed on all patients who received hand and/or foot PUVA 2002-2007 in the Northern Health and Social Care Trust (NHSCT), Northern Ireland. RESULTS: Thirty patients met the inclusion criteria for the study. The mean number of treatments, maximum single UVA dose, and cumulative dose, were 18.4, 4.2 J/cm2, and 48.3 J/cm2, respectively. A positive response to treatment occurred in 51.3% of patients, which fell short of the 70% standard set. In a multivariate logistic regression analysis, number of treatments (P=0.04) and maximum single UVA dose (P=0.03) were the only variables associated with positive treatment outcome. The response was not influenced significantly by skin type, concurrent topical treatments, or cumulative UVA dose. Limitations to the study: Small patient numbers may have prevented the statistical significance of individual variables. CONCLUSIONS: UV dose increments should be clearly defined to avoid excess caution at the expense of an adequate patient response, and a minimum of 20 treatments administered to all patients, if tolerated.

Hand-foot skin reaction in patients treated with sorafenib: a clinicopathological study of cutaneous manifestations due to multitargeted kinase inhibitor therapy.

BACKGROUND: Hand-foot skin reaction is a distinctive cutaneous side-effect of antineoplastic kinase inhibitor-targeted therapy. Severe hand-foot skin reaction requires postponement of treatment or dose reduction. Histopathological studies of skin toxicity associated with kinase inhibitors are currently unavailable. OBJECTIVES: To report the clinical and histopathological findings of hand-foot skin reaction produced by the multikinase inhibitor sorafenib. METHODS: Nine patients with metastatic carcinoma-seven with renal cell carcinoma (RCC), one with melanoma and one with hepatocellular carcinoma (HCC)-received continuous, oral sorafenib 400 mg twice daily. Hand-foot skin reaction was defined and graded according to National Cancer Institute Common Toxicity Criteria 3.0. Biopsies from lesions of erythematous scaly or blistering skin were obtained from five cases (four RCC and one HCC). RESULTS: Seven of the nine (78%) patients developed hand-foot skin reaction characterized by well-demarcated, tender, erythematous papules and plaques with greyish blisters or hyperkeratotic, callus-like formations on palmoplantar surfaces and distal phalanges. Skin biopsy of hand-foot skin reaction lesions revealed epidermal acanthosis, papillomatosis, parakeratosis, dispersed dyskeratotic cells and keratinocyte vacuolar degeneration. Other skin toxicities included angular cheilitis, seborrhoeic dermatitis and perianal dermatitis. CONCLUSIONS: The clinical manifestations and histopathological features of sorafenib-induced skin reactions are unique. The most relevant histopathological findings of hand-foot skin reaction include keratinocyte vacuolar degeneration, the presence of intracytoplasmic eosinophilic bodies, and intraepidermal blisters in the stratum malpighii. Further studies are warranted to elucidate the mechanisms of this novel multitargeted kinase inhibitor-associated skin reaction.

UVA1 phototherapy for cutaneous diseases: an experience of 92 cases in the United States.

BACKGROUND: The efficacy and safety of UVA1 (340-400 nm) phototherapy were established by studies from European countries. PURPOSE: Evaluate experience with UVA1 phototherapy for patients with cutaneous diseases in the United States. METHODS: A retrospective analysis of 92 cases of UVA1-treated cutaneous conditions from four medical centers in the United States was performed. RESULTS: Two-third of the patients showed a fair to good response (26-100% improvement) and one-third of the patients showed a poor response (0-25% improvement). Diseases with a moderate to good response (51-100% improvement) included scleredema adultorum, hand or foot dermatitis, atopic dermatitis, morphea (medium or medium- to high-dose UVA1), systemic sclerosis, and urticaria pigmentosa. Besides tanning, other adverse effects were found in 15% of patients, which include pruritus, erythema, tenderness, and burning sensation. Patients with skin types I-III responded better that those with a darker skin type. CONCLUSION: UVA1 phototherapy is a useful and well-tolerated treatment option for a variety of skin conditions.

Pápulas queratósicas acrales / Acral keratotic papules

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Necrolytic acral erythema in Egyptian patients with hepatitis C virus infection.

BACKGROUND: Necrolytic acral erythema (NAE) is a distinctive skin lesion that was first described in 1996 with only few cases being reported, mostly from Egypt. It is unique in its acral distribution and exclusive association with hepatitis C virus (HCV) infection. METHODS: Twenty-three patients (mean age 41.7 +/- 11.5 years; M:F 10:13) with clinical features consistent with NAE were enrolled in a 3-year period. Five of those were known HCV-infected individuals and 18 were referred by the dermatologist for evaluation and HCV screening. Liver function tests, serum zinc, hepatitis B markers, HCV antibodies and HCV-RNA were tested. All patients were subjected to skin biopsy examination; five lesional biopsies were selected for electron microscopic examination and capillary endothelium was scanned for hepatitis C viral particles. An additional five patients were subjected to detection of HCV-RNA in their skin biopsies by polymerase chain reaction. All patients received oral zinc sulfate supplementation while interferon-alpha therapy combined with ribavirin was available for four patients. RESULTS: Most NAE patients were adults (91.3%) and the skin lesions were predominantly chronic (78.3%), with affection of the dorsa of toes and/or feet in all cases. Skin biopsies showed hyperkeratosis, psoriasiform epidermis and upper epidermal necrosis. Electron microscope examination demonstrated clumped tonofilaments in the keratinocytes, yet HCV-RNA could not be detected in the skin lesions of examined cases. Interferon-alpha combined with ribavirin caused regression of skin lesions in three patients and complete clearance in one patient. Some improvement was induced by oral zinc administration. CONCLUSION: Necrolytic acral erythema is considered to be a cutaneous marker for HCV infection. The majority of patients are diagnosed by dermatologists. Therefore, improved awareness of this cutaneous lesion should prompt early diagnosis and treatment of HCV, which should in turn cure the lesion and prevent progression of liver disease.

Utility of histopathologic analysis in the evaluation of onychomycosis.

Onychomycosis is a common problem seen in clinical practice. Given the differential diagnosis of dystrophic nails, it is helpful to obtain a definitive diagnosis of dermatophyte infection before initiation of antifungal therapy. Potassium hydroxide preparation and fungal culture, which are typically used in the diagnosis of these infections, often yield false-negative results. Recent studies have suggested that nail plate biopsy with periodic acid-Schiff stain may be a very sensitive technique for the diagnosis of onychomycosis. In this article, we review the literature on the utility of histopathologic analysis in the evaluation of onychomycosis. Many of these studies indicate that biopsy with periodic acid-Schiff is the most sensitive method for diagnosing onychomycosis. We propose that histopathologic examination is indicated if the results of other methods are negative and clinical suspicion is high; therefore, it is a useful complementary technique in the diagnosis of onychomycosis.

Ultraviolet-free phototherapy.

BACKGROUND: Ultraviolet (UV) radiation phototherapy has been used for decades in the management of common skin diseases. On the other hand, UV radiation is a complete carcinogen and as a consequence, UV phototherapy is usually not used for the long-term management of children and young adults and in combination with topical or systemic immunosuppressants. PURPOSE: The therapeutic effectiveness of a new UV-free irradiation device in the treatment of patients with atopic hand and/or foot eczema was studied. METHODS: In a single-blinded trial 10 patients with atopic hand and/or foot eczema were treated with a sham irradiation device and with the new developed UV-free irradiation device DermoDyne during the following 4 weeks. All irradiation's lasted 30 min per treatment three times weekly. RESULTS: UV-free irradiation was found to induce a significant clinical improvement of atopic hand and foot eczema (P = 0.0001) in marked contrast to the sham-irradiation (P = 0.39). CONCLUSION: Our studies demonstrate that visible light can be successfully used for the treatment of patients with atopic eczema.

PUVA-gel vs. PUVA-bath therapy for severe recalcitrant palmoplantar dermatoses. A randomized, single-blinded prospective study.

BACKGROUND/PURPOSE: In order to avoid unwanted effects of systemic psoralen and ultraviolet A (PUVA) therapy, various topical PUVA treatment modalities have been developed and are being increasingly used. However, up to now very few controlled studies comparing the therapeutic efficacy of different topical photochemotherapy modalities are available. Thus, the aim of our study was to compare the clinical efficacy of conventional PUVA-bath therapy to topical PUVA-gel therapy in patients with recalcitrant dermatoses of the palms and soles. METHODS: Twenty patients with severe palmoplantar dermatoses or localized psoriatic plaques were enrolled in our observer-blinded, randomized half-sided study. The treatment modalities compared were: (i) aqueous 8-methoxypsoralen (8-MOP)-containing gel plus broadband UVA irradiation (PUVA-gel therapy) and (ii) 8-MOP bath of the hands and/or feet plus broadband UVA (PUVA-bath therapy). RESULTS: On the body half, which was randomized to PUVA-gel therapy, the median Area and Severity Index for palmoplantar dermatoses (ASIppd) decreased from 28 (range 6-56) to 1.5 (range 1-37, P = 0.00) after a median 33 (13-49) irradiations compared with a reduction from 26.5 (range 6-52.5) to 1.5 (range 0-38, P = 0.00) for PUVA-bath therapy. Both improvements of ASIppd scores were found to be statistically significant, with no significant difference between PUVA-gel and PUVA-bath therapy. Severe phototoxic reactions such as strong erythema, blistering and/or pain were not observed in any patient. CONCLUSION: PUVA-gel therapy seems to be an effective therapeutic alternative to conventional PUVA-bath therapy in treating localized dermatoses of the palms and soles. The advantage of PUVA-gel therapy is reduced organizational efforts and expenses.

Allergic contact dermatitis to propolis.

A 35-year-old Asian woman was referred to the dermatology clinic with a 2-week history of enlarging, fluid-filled, pruritic lesions on the right foot. The affected area had a recent history of minor trauma for which the patient applied an over-the-counter propolis ointment. At presentation, the patient was also noted to have been using the following, as prescribed by her primary care physician: valacyclovir, ciprofloxacin, terbinafine cream, mupirocin ointment, and 2% hydrocortisone cream. No clinical improvement was observed with these agents. Examination revealed grouped erythematous papules progressing into vesicles and bulla on the lateral side of the right foot. A KOH scraping was negative. We diagnosed the patient with allergic contact dermatitis to propolis.

[Keratosis lichenoides chronica. Bath PUVA therapy]. / Keratosis lichenoides chronica Erfolgreiche Therapie mit Bade-PUVA.

We describe the case of a 51-year-old male patient with characteristic lesions of keratosis lichenoides chronica confined to the back of his hands and feet. The lichenoid papules, linear hyperkeratotic ridges and erythematosquamous plaques appeared first in early childhood and recurred after a short episode of spontaneous remission. They didn't respond to various topical treatment modalities over the years. After a local PUVA therapy all lesions disappeared with no recurrence for over two years now. Our case report indicates a new promising indication for bath-PUVA-therapy.