Harnessing the skin-thyroid connection for wound healing: a prospective controlled trial in guinea pigs.

BACKGROUND: Different elements of the hypothalamic-pituitary-thyroid axis have been found to be implicated in the normal physiology of the human skin. Their effects on wound healing and hair growth in rats have been described previously. There is close homology between the thyroid hormone receptors in humans and guinea pigs. AIM: To assess the effect of different doses of topical 3,3',5-triiodo-L-thyronine (T3) and recombinant human thyroid-stimulating hormone (TSH) on wound healing in guinea pigs. METHODS: Wounds were dressed every other day for 7 days, during which clinical measurements of the wounded areas were performed. Histological examination was performed at the end of the study. RESULTS: Application of high and low concentrations of topical T3 but not TSH demonstrated a significant dose-dependent reduction in the wound surface area through a process of contraction. The main significant histological result was an increase in the hair-follicle count. CONCLUSION: Topical T3 enhances wound healing in guinea pigs, primarily by wound contraction. As this is a critical stage in healing of chronic ulcers, topical T3 could be a useful treatment for wounds.

A rationale for systemic treatment in onychomycosis with negative results on fungal examination.

BACKGROUND: Fungal infection of the nail affects millions of people worldwide, and has an estimated prevalence of about 10% of the general population. Laboratory confirmation of fungal infection is currently accepted as a requirement before initiation of antifungal treatment in clinical practice. AIM: To examine the rationale for systemic treatment in cases of clinical onychomycosis with negative results on fungal examination (potassium hydroxide test and fungal culture). METHODS: In total, 147 patients with suspected clinical toenail onychomycosis but with negative results on fungal examination underwent up to three consecutive fungal examinations of the affected nails. Patients who were negative after these examinations underwent a fourth set of investigations, including PCR. RESULTS: Of the 147 cases initially thought to be negative, 138 (94%) were rated as positive after up to four consecutive sets of laboratory mycological investigations including PCR. Trichophyton rubrum was by far the commonest dermatophyte cultured from all samples. CONCLUSIONS: In the majority of cases of initially negative examinations, consecutive laboratory fungal tests will eventually produce positive results. These findings suggest that systemic antifungal treatment should be started in patients with suspected fungal infections, even if they have negative laboratory fungal examinations.

High prevalence of malignant melanoma in Israeli patients with Parkinson's disease.

The risk of melanoma is higher in patients with Parkinson's disease (PD) than in the general population. Whether the association is disease related or treatment related is unclear. The objective of this study was to assess melanoma prevalence in PD patients in Israel using active dermatologic screening. Consecutive patients with idiopathic PD were recruited by 12 Israeli centers. A movement disorder specialist assessed the severity of PD and obtained a medical, neurological, and medication history. Subsequently, a dermatologist assessed melanoma risk factors, recorded a dermatologic history, proactively performed a whole-body skin examination, and biopsied suspicious skin lesions. Of the enrolled patients (n = 1,395, mean age 69.5 ± 10.6 years, mean PD duration 7.3 ± 6.0 years), 95.3% were treated with dopaminergic agents. Biopsies revealed 8 patients with melanoma in situ and 1 with invasive malignant melanoma; 14 patients reported a melanoma prior to enrollment. The observed 5-year limited duration prevalence of melanoma in PD patients was 4.4 times greater (95% CI 2.6-7.6) than expected from melanoma prevalence in an age- and sex-matched cohort from the Israel National Cancer Registry. The increase was accounted for by an elevated prevalence of melanoma in situ [relative risk 12.5 (95% CI 6.7-23.2)]. Occurrence of melanoma did not correlate with levodopa therapy or time of onset of PD. Melanoma prevalence in PD patients was higher than expected in the general Israeli population. This was not related to levodopa treatment. PD patients should be actively screened for melanoma on a routine basis.

Liposomal amphotericin B treatment of cutaneous leishmaniasis due to Leishmania tropica.

BACKGROUND: Cutaneous leishmaniasis (CL) is endemic in Israel, and in the past, has been attributed almost exclusively to Leishmania major. Over the last decade or so, an increase in Leishmania tropica (L. tropica) infections has occurred in several regions of Israel. Topical treatment of Old World CL is usually the rule, however, in some cases systemic treatment is indicated. Liposomal amphotericin B (L-AmB) is efficacious and safe for treating visceral leishmaniasis but its role in treating various forms of CL is yet to be defined. In this study, we summarize the efficacy and safety of L-AmB treatment in a series of Israeli patients with L. tropica infection. METHODS: Cases of PCR-proven CL caused by L. tropica were treated in an outpatient setting. Treatment schedule consisted of five consecutive days of 3 mg/kg L-AmB, followed by a sixth dose on day 10. RESULTS: Thirteen consecutive patients (11 men, two women), received L-AmB. Mean age was 15.3 years; of the 13 patients, 85% had facial lesions. Six had previously failed intralesional sodium stibogluconate treatment and four had failed topical paromomycin treatment. Eleven of 13 patients (84%) achieved complete clinical cure within 2 months. Mean follow-up of 11 months revealed no relapses. Side effects were mild and none terminated treatment prematurely. LIMITATIONS: A non-randomized study, with a small number of patients. CONCLUSION: Liposomal amphotericin B treatment for L. tropica is effective, well tolerated and cost beneficial in countries where cost of hospital-care is significant.

The role of therapeutic plasma exchange in pemphigus vulgaris.

BACKGROUND: The treatment of pemphigus, an autoimmune bullous disease, is based on the combination of corticosteroids and adjuvant therapies, such as immunosuppressive drugs, anti-inflammatory drugs and immunomodulatory procedures, such as intravenous immunoglobulin and therapeutic plasma exchange (TPE). OBJECTIVE: This study aims to assess our experience with TPE as a steroid-sparing modality in moderate and severe intractable pemphigus patients. METHODS: A retrospective evaluation for all intractable pemphigus patients treated by TPE in a university-affiliated tertiary referral medical centre between the years 1998 and 2008. Treatment protocol included three TPE treatments weekly for 1-3 months, combined with monthly pulse therapy of dexamethasone and/or cyclophosphamide. Maintenance therapy was based on once/bi weekly TPE treatments or monthly intravenous immunoglobulin. RESULTS: Seven patients were included in the study, four with severe pemphigus vulgaris and three with moderate disease. Six of the seven patients responded to TPE: Four patients (57%) achieved complete remission and two patients (28%) achieved partial remission on minimal therapy. Mild adverse effects related to TPE were observed in two patients and included dizziness and mild headache. CONCLUSION: TPE is a well-tolerated effective steroid-sparing agent in recalcitrant pemphigus patients.

Low-dose methotrexate treatment for moderate-to-severe atopic dermatitis in adults.

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease. Methotrexate (MTX) was suggested as an effective treatment option in cases of moderate-to-severe atopic dermatitis. This study assessed the efficacy and safety of treatment with low weekly doses of methotrexate for moderate-to-severe AD in adults. METHODS: Twenty adult patients with moderate-to-severe AD were included in this retrospective study. Those patients were unresponsive to topical treatments, antihistamines and at least one of the second-line treatments. MTX in low weekly doses of 10-25 mg was administered orally or intramuscularly with folic acid supplementation 5 mg per week for at least 8-12 weeks. The response to treatment was evaluated by change in SCORAD (SCORing Atopic Dermatitis), DLQI (Dermatology Quality of Life Index) and the global assessment of the clinical response score. RESULTS: After 8-12 weeks of treatment, we observed an objective response in most patients. There were 16 responders and 4 non-responders. The mean SCORAD and DLQI decreased by 28.65 units (44.3%) and 10.15 units (43.5%), respectively. The first improvement was observed after a period ranging from 2 weeks to 3 months (mean 9.95 w +/- 3.17). Treatment was more effective in adult onset AD than in childhood onset. Tolerance of treatment was good. However, nausea and an increase of liver enzymes were observed in 5 patients and 3 of them required a transient discontinuation of MTX. One patient developed peripheral neuropathy, which was resolved several weeks after the discontinuation of MTX. CONCLUSION: MTX seems to be an effective and safe second-line treatment for patients with moderate-to-severe atopic dermatitis. A randomized, controlled study is warranted.

Silicone breast implant rupture presenting as bilateral leg nodules.

Gross migration of silicone gel from ruptured breast implants is a rare event. It is associated with extravasation of gel into the breast parenchyma, and to distant locations such as the abdominal wall and inguinal areas. This silicone deposits present as subcutaneous nodules and cause a local reaction known as siliconoma. We evaluated a 56-year-old woman who presented with a 2-year history of painful, firm and ill-defined subcutaneous nodules on the medial aspect of the shins and ankles. Her medical history was notable for bilateral breast augmentation with silicone implants 30 years before presentation. Although there were no signs or symptoms on breast examination, ultrasonography and magnetic resonance imaging confirmed that both implants had ruptured. Histological examination of a punch biopsy from a nodule on the shin found lobular granulomatous panniculitis. An excisional biopsy of the lesion was analysed by scanning electron microscopy and was found to contain silicone. This is a rare case of gross migration of silicone to the shins, originating from ruptured breast implants. To our knowledge, there is no previous report of silicone migration to such a distant location. We discuss the common presentation of silicone migration and highlight the importance of awareness among dermatologists and plastic surgeons about this unusual occurrence.

Treatment of cutaneous leishmaniasis with intralesional sodium stibogluconate.

BACKGROUND: Cutaneous leishmaniasis is endemic in Israel. Leishmania major is the most prevalent species that cause cutaneous leishmaniasis. Current treatment options are limited and there are few investigations in search of alternative ones. OBJECTIVE: This study aims to assess our experience with intralesional sodium stibogluconate (SSG) in the treatment of cutaneous leishmaniasis. METHODS: A retrospective evaluation for all adult cases of cutaneous leishmaniasis treated by intralesional and intravenous SSG (Pentostam, GlaxoSmithKline) between 2004 and 2006 was performed, for cases referred to a tertiary care university-affiliated medical centre in Israel. Intralesional SSG was injected at 0.5 mL per lesion (50 mg). Treatment was repeated every 2-3 weeks for a total of 12 weeks. Intravenous SSG was administered at a dose of 20 mg/kg for 10-20 days. RESULTS: Thirty-three cases of cutaneous leishmaniasis were treated with intralesional SSG during the study period. The patients consist of 26 males and 7 females, mostly Israeli military personnel, and there were a total of 93 lesions. Within 3 months from treatment onset, 91% (30/33) had completed healing of the cutaneous lesions after an average of 3 treatments (range 1-6). Side-effects were mild and were mostly pain during injection, with two patients developing mild local site reaction after the injection. CONCLUSIONS: Intralesional SSG treatment is safe, effective and well tolerated with minimal side-effects.

New criteria for the laboratory diagnosis of nondermatophyte moulds in onychomycosis.

BACKGROUND: Nondermatophyte moulds (NDM) may be found as aetiological agents or as contaminants in onychomycosis. The classic and most used criteria for the diagnosis of NDM are those established by English in 1976. OBJECTIVES: The aim of this article is to re-evaluate the laboratory criteria for the diagnosis of NDM in onychomycosis. PATIENTS AND METHODS: Patients with suspected NDM of the nail underwent five consecutive examinations by both KOH and mycological culture; at the first visit, three samples from the affected nail were taken and were examined separately. Later those patients underwent four consecutive examinations; during this stage only a single sample for both KOH and culture was taken. We compared the culture results obtained from the three nail samples obtained at the first visit with the results from the four consecutive visits. RESULTS: We noted a clear trend showing that as the number of positive cultures increases (one to three cultures) during the first examination, the percentage of subsequent positive cultures, taken during the four consecutive visits, also increased. CONCLUSIONS: We suggest that when NDM infection is found in the first culture, the patient should be re-examined in a subsequent visit in which three separate samples are taken from the affected nail. If NDM is confirmed in all three cultures, the diagnosis of NDM is established. Treatment should be recommended in patients who show positive results in all three cultures.

Pancreatic panniculitis and carcinoma of the pancreas.

Pancreatic panniculitis is a rare complication of carcinoma of the pancreas, most often accompanying the rare acinar cystadenocarcinoma. It presents with painful erythematous subcutaneous nodules typically located on the leg. We present a case of a 79-year-old man with neuroendocrine carcinoma of the pancreas and liver metastasis, who developed painful subcutaneous nodules on his shins. Laboratory values included a raised lipase level with normal amylase level and peripheral eosinophilia. The patient was treated with nonsteroidal anti-inflammatory drugs, dexamethasone and antibiotics, with resolution of the dermatological symptoms.

Onycomycosis due to artificial nails.

BACKGROUND: The use of artificial nails (ANs) as part of nail-care cosmetics is very popular. Several side effects and complications, such as contact dermatitis and bacterial and fungal infections, have been reported in patients using ANs. Objective The purpose of this study was to identify the fungal pathogens in nail abnormalities appearing in patients with ANs. METHODS: We evaluated 68 patients suffering from nail changes and paronychia, which appear after removal of ANs. Mycological samples were obtained from two sites: distal parts of the involved nail and the proximal nail fold. KOH examination and fungal culture were used for detection and identification of fungal infection. RESULTS: Mycological results from the distal part of the nail showed positive KOH test in 57 cases (83.8%), and culture was positive in 67 patients (98.5%). Mycological results obtained from the proximal nail fold showed positive KOH test in 36 patients (52.9%); in 36 of the cases, culture was positive. Candida spp. were the most common pathogen. Both KOH and culture results were significantly better while sampling from the distal part of the nail compared with sampling from the proximal nail fold (P = 0.0001). CONCLUSION: Onychomycosis was found to be very common in nail changes due to ANs, leading to an increased risk of transmitting microbial infections. Therefore, health care personnel and workers in the food industry should avoid using ANs.

Toenail abnormalities and onychomycosis in chronic venous insufficiency of the legs: should we treat?

BACKGROUND: Toenail manifestations of chronic venous insufficiency (CVI) may often mimic the nail changes of onychomycosis. The current study aims to determine the frequency of toenails deformations in patients with CVI, onychomycosis prevalence among deformed toenails and the outcome of itraconazole treatment. METHODS: Patients with clinical evidence of (CVI) were enrolled. All patients with toenails deformations and proven onychomycosis were treated by itraconazole pulse therapy for 4 months and then followed-up for additional 5 to 6 months. RESULTS: Forty-four patients with CVI entered the study. Thirty-seven patients (84%) had nail deformations; 28 of 37 patients (75%) had onychomycosis; and 24 patients completed the follow-up period. Total cure was achieved in 6 of 24 patients (25%), and 14 patients (58%) had no improvement. Patients' age and CVI duration were significantly correlated to onychomycosis cure rate. CONCLUSIONS: Nail deformations are more prevalent in CVI patients (84%) then in the general elderly population, and 75% of affected nails had also onychomycosis. In these patients, itraconazole achieved only 25% total cure rate compared with the 60% to 70% cure rate commonly cited in the literature, probably due to irreversible nail deformity caused by the CVI and due to the thickened nail that prevented penetrance of itraconazole into the nail plate. Therefore, before antifungal treatment is started for onychomycosis in patients with CVI, especially in older patients, the caregiver must stress out that the final outcome might not be as desirable as in pure onychomycosis patients.

Very late antigen-1 in psoriasis: an immunohistochemical study.

BACKGROUND: Currently, psoriasis is thought to be an inflammatory response to an antigenic stimulation, in which angiogenesis plays a fundamental role. Very late antigen-1 (VLA-1) is a beta(1) integrin collagen receptor that is up-regulated in many angiogenic processes. Data on its role in psoriasis are sparse. OBJECTIVE: In a prospective study, we evaluated the staining of VLA-1 in lesional skin from patients with psoriasis and atopic dermatitis. MATERIAL AND METHODS: Frozen sections from skin biopsies of patients with chronic plaque-type psoriasis (n = 18) and chronic atopic dermatitis (n = 7) were stained with a monoclonal antibody to VLA-1. The number of blood vessels stained with VLA-1 and the staining intensity were evaluated. These were correlated with the histologic features. RESULTS: The absolute number of blood vessels was found to be similar in the atopic and psoriatic samples. However, the number of vessels stained with anti-VLA-1, as well as the staining intensity, was shown to be significantly higher in the psoriasis group (P < 0.05). Differences between psoriatic lesions showing typical histological features of psoriasis and those showing features that overlap with dermatitis were found as well. CONCLUSIONS: Expression of VLA-1 was found significantly higher in lesional dermal blood vessels of psoriatic patients compared with atopic patients. These findings suggest a possible role for VLA-1 in the pathological angiogenesis of psoriasis. It may be an additional tool for establishing the diagnosis of psoriasis and provide a basis for new strategies in the treatment of psoriasis.

Collection of fungi samples from nails: comparative study of curettage and drilling techniques.

BACKGROUND: Onychomycosis is a common problem. Obtaining a positive laboratory test before treatment is important in clinical practice because the treatment of onychomycosis requires expensive oral antifungal therapy with potentially serious side-effects. OBJECTIVE: The purpose of this study was to compare curettage and subungual drilling techniques of nail sampling in the diagnosis of onychomycosis. METHODS: We evaluated 194 patients suffering from distal and lateral subungual onychomycosis and lateral subungual onychomycosis using curettage and subungual drilling sampling techniques. Nail samples were obtained in each case from proximal, medial and distal parts of the nail. KOH examination and fungal culture were used for detection and identification of fungal infection. RESULTS: With each technique, the culture sensitivity improved as the location of the sample was more proximal (drilling proximal vs. distal, chi(2) = 5.15, P = 0.023; curettage proximal vs. distal, chi(2) = 4.2, P = 0.041). In each sample location, the drilling technique has a better culture sensitivity (drilling vs. curettage proximal, chi(2) = 11.9, P = 0.001; drill vs. curettage distal, chi(2) = 13.7, P < 0.0001). Trichophyton rubrum was by far the most common pathogen detected by both techniques from all sampling sites. CONCLUSION: The drilling technique was found to be statistically better than curettage at each site of sampling. With each technique, we found that the culture sensitivity improved as the location of the sample was more proximal. More types of pathogens were detected in samples taken by both methods from proximal parts of the affected nails.

Mycosis fungoides associated with B-cell malignancies.

BACKGROUND: The coexistence of mycosis fungoides, a peripheral T-cell lymphoma, and B-cell malignancies or Hodgkin's lymphoma in the same patient is unusual. Most descriptions are isolated case reports and case series are strikingly sparse. OBJECTIVES: To detect cases of mycosis fungoides associated with B-cell malignancies or Hodgkin's lymphoma and to analyse the characteristics of and the interplay between the lymphoproliferative neoplasms. METHODS: Patients with mycosis fungoides who had B-cell malignancies or Hodgkin's lymphoma were selected from among 398 patients either treated or followed up in two tertiary medical centres during a 7-year period. RESULTS: Eleven patients with mycosis fungoides and B-cell malignancy were detected (seven of non-Hodgkin's lymphoma, three of chronic lymphocytic leukaemia, one of multiple myeloma). No case of Hodgkin's lymphoma was found. In seven patients the mycosis fungoides preceded the B-cell malignancy whereas in four it was the B-cell malignancy which occurred first. The time elapsed between onset of the two malignancies ranged from 4 to 22 years (average: 12 years). Patients who had mycosis fungoides as the first neoplasm presented with earlier stages of mycosis fungoides (four of seven: IA, three of seven: IB) than those who had mycosis fungoides as their second neoplasm (of four, one: IB, one: folliculotropic, two: IIB). Among the four patients in whom the appearance of mycosis fungoides followed the B-cell malignancy, three had been treated with multiagent chemotherapy. Two patients who presented with early-stage mycosis fungoides (IA) as the first lymphoma developed mycosis fungoides tumours after becoming immunosuppressed. In two patients infiltrates composed of both malignant T- and B-cell populations were found in a single biopsy. One showed two distinct populations of the malignant cells in the skin tumour, thus constituting a classical composite lymphoma of mycosis fungoides and chronic lymphocytic leukaemia, while in the other patient the two malignant populations of marginal B-cell lymphoma and mycosis fungoides (as evidenced by both phenotypic and genotypic findings) were intermingled. CONCLUSIONS: This case series indicates that while the coexistence of Hodgkin's lymphoma and mycosis fungoides is extremely rare, the association of mycosis fungoides and B-cell malignancies is not as rare as reflected in the literature, with non-Hodgkin's lymphoma constituting the most common associated B-cell malignancy. In this series as well as in the cases reported in the literature mycosis fungoides usually preceded the development of B-cell malignancies, which may be in accordance with previous reports of an increased risk of developing a second haematological neoplasm. The importance of a competent immune system for patients with mycosis fungoides is well demonstrated in these cases. It is suggested that for greater precision the criteria for diagnosis of composite lymphoma of the skin should include both phenotypic and genotypic features.

The role of IVIg treatment in severe pemphigus vulgaris.

BACKGROUND: High-dose intravenous immunoglobulin (IVIg) has become a part of the treatment armentarium in pemphigus vulgaris (PV). Some consider IVIg as an adjuvant steroid sparing agent in PV, while others as disease modifying that can be used as monotherapy. METHODS: We report our experience with a series of 12 PV patients with severe disease treated with IVIg as an adjuvant therapy. RESULTS: Ten of 12 patients (83%) showed response to six cycles of IVIg, six (50%) having complete remission and four (33%) having a partial response. This response rate is concordant with previous reports. The therapy was well tolerated. In all 12 patients, treatment with IVIg allowed a gradual reduction of prednisone dose compared with baseline levels. CONCLUSION: IVIg treatment was beneficial as a steroid sparing agent in our series of patients with severe PV.

UVB therapy of pityriasis lichenoides--our experience with 29 patients.

BACKGROUND: Pityriasis lichenoides comprises a clinical and pathological spectrum of disorders. So far no highly effective treatment has been reported. Previous small studies have suggested that ultraviolet B (UVB) is a good alternative. METHODS: This is a retrospective analysis of 29 pityriasis lichenoides patients treated in our institution with broad- or narrow-band UVB during the period 1996-2002. Twenty-one of these patients had one or more previous unsuccessful treatments. RESULTS: Complete response was achieved in 93.1% in both treatment groups, with 73% of them still relapse free after a mean follow-up of 58 and 38 months in broad- and narrow-band UVB treatment groups, respectively. Mild side-effects were observed in about one-third of the patients. CONCLUSION: We believe both forms of UVB are a good option for pityriasis lichenoides and should be considered as the first line in generalized cases interested in treatment.

UVB in the management of early stage mycosis fungoides.

BACKGROUND: Several options for treatment of early mycosis fungoides (MF) offer similar success rates. Previous small studies have shown UVB to be at least as effective as PUVA. OBJECTIVE: To summarize our experience with UVB treatment of early MF. METHODS: A retrospective analysis of early-stage MF patients treated by narrow band (NB) or broad band (BB) UVB in our institution between 1996 and 2002. Most patients achieving complete response (CR) were put on maintenance until natural sun exposure was possible and followed up every 3-6 months. The results were compared to those previously reported regarding PUVA. RESULTS: Sixty-eight and 43 patients were treated by NB and BB UVB, respectively. Eighty-six per cent (84 and 89% in NB and BB UVB groups, respectively) of IA and 71% (78 and 44% in NB and BB UVB groups, respectively) of IB patients achieved CR within a mean of 12.8 and 10.6 weeks, respectively. When maintenance was stopped, 65 and 30% had not relapsed after an average follow up of 27 and 222 weeks, respectively. Non-relapse rate was 33 and 48% for those having had vs. those not having had maintenance, respectively. CONCLUSIONS: Our results are comparable to all previously reported for skin-targeted treatments, including PUVA and, to our belief, reflect the nature of early MF, in which CR can probably be achieved in most of the patients. Among the responding patients there is no relapse during prolonged follow-up in about one third of the cases. Thus, we believe treatment should be stopped completely following first CR induction and maintenance treatment should be considered for relapsing patients only. Both broad and narrow UVB options are good and future choices should be made on the basis of short- and long-term side-effects.