Is there any relation between serum insulin and insulin-like growth factor-I in non-diabetic patients with skin tag?

BACKGROUND: Skin tags are common benign lesion occurring mainly on the neck and major flexures as a small soft pedunculated protrusion. This study evaluate insulin and insulin-like growth factor-I (IGF-I) in non-diabetic ones. METHODS AND MATERIALS: A case-control study was conducted in non-diabetic persons. Comparing insulin and IGF-I between matched cases (n = 40) and controls (n = 40) by radioimmunoassay test. Cases and controls were recruited from patients consecutively seen at an academic outpatient dermatology clinic. RESULTS: The insulin level in patients with skin tags was significantly higher than controls (P = 0.00) but IGF-I level was not significantly different (P = 0.43). CONCLUSION: These results show an increased insulin level in non-diabetics ones and overall importance of insulin effect in pathogenesis of skin tags.

Proton pump inhibitors: predisposers to Alzheimer disease?

The abnormal processing of amyloid-beta peptide (A beta) and resultant formation of fibrillar A beta (fA beta) are major events in the pathogenesis of Alzheimer disease (AD). Microglia as the phagocytic cells of the brain can engulf and digest fA beta within their acidic lysosomes. The lysosomes of AD patients are less acidic and therefore less capable of clearance of fA beta. Vacuolar proton pumps (V-ATPases) which are found abundantly in microglia and macrophages, acidify lysosomes by pumping protons into these structures. Proton pump inhibitors (PPIs) can inhibit V-ATPases of the lysosomes. These drugs are shown to penetrate the blood-brain barrier in animals. PPIs are consumed for long periods in conditions such as gastroesophageal reflux disease, with the resultant exposure of the human brain to the substantial amounts of PPIs. We hypothesize that by blocking the V-ATPases on microglial lysosomes, PPIs may basify lysosomes and hamper degradation of fA beta. Chronic consumption of PPIs may thus be a risk factor for AD.

Rubeosis faciei diabeticorum: a common, but often unnoticed, clinical manifestation of diabetes mellitus.

In this clinical image, we present the picture of a diabetic patient with rubeosis faciei diabeticorum, a relatively common, but usually unnoticed, microangiopathic complication of diabetes mellitus that could herald other more notorious microangiopathic complications of diabetes mellitus, such as retinopathy. This case will help other physicians to consider rubeosis faciei diabeticorum whenever they face similar cases.

The remarkable beneficial effect of adding oral simvastatin to topical betamethasone for treatment of psoriasis: a double-blind, randomized, placebo-controlled study.

BACKGROUND: Psoriasis is a common chronic inflammatory disease with unpredictable prognosis. Given the immunomodulatory effects of statins, the present study was conducted to determine whether the addition of orally administered simvastatin to the topical betamethasone, a standard antipsoriatic treatment, can produce a more powerful therapeutic response against this clinical conundrum. METHOD: In a double-blind study, 30 patients with plaque type psoriasis were randomly divided into two equal treatment groups. Group 1 received oral simvastatin (40 mg/d) plus topical steroid (50% betamethasone in petrolatum) for 8 weeks and group 2 received oral placebo plus the same topical steroid for the same time period. Psoriasis Area and Severity Index (PASI) score was checked before and at the end of the treatment period. RESULTS: PASI score decreased significantly in both groups, but the decline of PASI score was more significant in patients who received simvastatin (Mann-Whitney test; P-value = 0.001). No side effect or any laboratory abnormality was detected in patients. CONCLUSION: Our work, which is the first double-blind, randomized, placebo-controlled study on this subject, shows that oral simvastatin enhances the therapeutic effect of topical steroids against psoriasis. The increased risk of cardiovascular accidents in psoriatic patients and the protective effect of statins against cardiovascular disease further encourages their use in the treatment of this clinical conundrum.

Self-inflicted non-healing genital ulcer: a rare form of factitious disorder.

Dermatitis artefacta is a factitious dermatological disorder with many forms of presentation that may occur on any part of the body. A diagnosis of dermatitis artefacta is often reached after rigorous and repeated investigations. Here we present the case of a 49-year-old single man complaining of a 4- month history of ulceration on the dorsal surface of the glans penis. In view of the unusual appearance of the lesion and the negative findings from clinical investigations, a diagnosis of dermatitis artefacta was made and the patient was referred for psychiatric evaluation. He was started on 20 mg/day of citalopram and titrated up to 40 mg/day by the 4th week, leading to complete remission in the following weeks. Thus, although rare, artefactual dermatitis should be considered in the differential diagnosis of unusual penile lesions.

Aloe vera in dermatology: a brief review.

Aloe vera Linne or aloe barbadensis Miller is a succulent from the Aloe family (400 different species), a tropical plant which is easily grown in hot and dry climates and widely distributed in Asia, Africa and other tropical areas. The use of aloe vera is being promoted for a large variety of conditions. The aim of this systematic review was to summarize all dermatology-oriented in vitro and in vivo experiments and clinical trials on aloe vera preparations. Extensive literature search were carried out to identify all in vitro and in vivo studies as well as clinical trials on the subject. Data were extracted from these in a predefined standardized manner. Forty studies were located. The results suggest that oral administration of aloe vera in mice is effective on wound healing, can decrease the number and size of papillomas and reduce the incidence of tumors and leishmania parasitemia by >90% in the liver, spleen, and bone marrow. Topical application of aloe vera is not an effective prevention for radiation-induced injuries and has no sunburn or suntan protection. It can be effective for genital herpes, psoriasis, human papilloma virus, seborrheic dermatitis, aphthous stomatitis, xerosis, lichen planus, frostbite, burn, wound healing and inflammation. It can also be used as a biological vehicle and an anti-microbial and antifungal agent and also as a candidate for photodynamic therapy of some kinds of cancer. Even though there are some promising results with the use of aloe vera for diverse dermatologic conditions, clinical effectiveness of oral and topical aloe vera is not sufficiently and meticulously explored as yet.

Administration of heparanase-III improves the survival and angiogenesis of rat skin autografts.

AIM: Heparanase, a glycohydrolase enzyme, cleaves heparan sulfate in the tissue matrix. Heparan sulfate degradation causes the release of angiogenic and growth factors, leading to angiogenesis. The aim of this paper was to evaluate the angiogenic effect of heparinase-III administration on skin autograft healing in rat. METHODS: Four groups of 14 adult male Charles River rats were enrolled. Full thickness skin autografts (15 mm in diameter) were made on the interscapular region of each rat. After 24 hours, 0.1 cc of heparanase, at the three concentrations of 0.1, 0.2, and 0.4 units, were injected intradermally into the grafts of each of the three case groups. The control group received an equal volume of the vehicle (buffered phosphate solution). After 5 days, biopsy specimens from skin grafts of 5 randomly selected rats of each group were submitted for histological studies. RESULTS: The concentration of vessels (with 5-50 mm in diameter) in the grafts of the groups receiving 0.2 and 0.4 units of heparanase-III was significantly more than that of the control group (100.43+/-11.24 and 95.85+/-12.44 vs 71.42+/-5.22 vessels/mm(2), P<0.05). The graft survival time of the group that received 0.2 U heparanase-III was significantly longer than that of the control group (15.43+/-0.72 vs 13.23+/-0.69 days; P<0.05). CONCLUSIONS: Heparanase-III administration improves the healing of rat skin autografts through induction of angiogenesis.

Serum magnesium concentrations in vitiligo patients.

Hypomagnesemia has been shown to contribute to oxidative stress and inflammation. This study was designed to evaluate the serum magnesium (Mg) concentration in vitiligo patients versus controls. Twenty-seven patients with vitiligo were enrolled in this study, along with 27 age and sex-matched healthy controls. The mean serum Mg concentrations in the case and control groups were 0.75 ± 0.07 and 0.77 ± 0.07 mmol/L, respectively. No significant difference in the mean concentrations of Mg between the two groups was noted (P = 0.95). However, interestingly, we noticed a positive correlation between serum Mg concentration and Vitiligo Area Severity Index (VASI) score as well as the total body surface area (TBSA) concerned by the disease. Further research on the role of Mg in vitiligo is therefore warranted.

Unexpected diminished innervation of epidermis and dermoepidermal junction in lichen amyloidosus.

BACKGROUND: Lichen amyloidosus is a localized, chronic, pruritic skin disease characterized by deposition of amyloid in the papillary dermis. The pathogenesis of the pruritus of lichen amyloidosus is largely unknown. OBJECTIVES: To determine any change in the nerve fibre density in lichen amyloidosus lesions as an explanation for itch. METHODS: Using an antibody to protein gene product (PGP) 9.5, the immunohistochemical analysis of the skin biopsies of 30 Hispanic patients with clinicopathologically proven lichen amyloidosus and of 11 healthy Hispanic controls matched for age, sex and site was performed. RESULTS: Unexpectedly, the mean amount of PGP9.5 stain, a measure for nerve fibre amount, for the healthy controls was higher than the lichen amyloidosus group both in the epidermis (P < 0.0019) and dermoepidermal junction (P < 0.0064). No change was observed in the papillary dermis. Furthermore, the proportion of area covered by PGP9.5 showed a significant decrease in the epidermis (P < 0.0024) and dermoepidermal junction (P < 0.0075) in lichen amyloidosus compared with healthy controls. Age, gender and body site were found not to be influencing factors in nerve fibre amounts in lichen amyloidosus samples. CONCLUSIONS: We speculate that the severe pruritus observed in lichen amyloidosus might be the result of the hypersensitivity of the remaining nerve fibres as a response to an unexplained neurodegeneration of the absent nerve fibres.

Nevus lipomatosus cutaneous superficialis of the groin arising in the fifth decade of life.

Nevus lipomatosus cutaneous superficialis (NLCS) is a rare malformation characterized by ectopic adipose tissue in the dermis. The lesion is usually present from birth or noticed in the first 2 decades of life. It occurs as sessile or pedunculated, domed nodular growths with a smooth, wrinkled, or cerebriform surface. Multiple lesions have a marked predilection for the gluteal region, lower back, and upper thigh, though solitary lesions may occur at unusual sites like the scalp, clitoris, and calf. An unusal case of NLCS is presented here where the solitary lesion occurred as a large exophytic growth arising at the groin in the fifth decade of life.

Association of angiokeratoma of the vulva with angioma serpiginosum.

Angioma serpiginosum is a rare benign vascular disorder usually beginning in childhood. It is characterized clinically by multiple minute, bright red to purple, grouped macules and histopathologically by an ectatic dilatation of capillaries. Angiokeratoma of the vulva is an uncommon lesion occurring in older women. It consists of purple papular lesions measuring less than 1 cm in diameter and characterizing histopathologically by hyperkeratosis, papillomatosis, acanthosis, and dilated vasculature in the papillary dermis.

The potential anti-xanthoma and anti-atherosclerotic effects of proton pump inhibitors.

Xanthoma and atherosclerosis are similar in having infiltrations of macrophages that have transformed into foam cells. The oxidized low-density lipoprotein (LDL) promotes adhesion of monocytes to endothelial cells by inducing expression of adhesion molecules on vascular endothelial cells. Macrophages transform into foam cells by incorporating oxidized LDL using several kinds of scavenger receptors. Very recently, it has been shown that LDL oxidation occurs within lysosomes in macrophages in atherosclerotic lesions and the increase of intra-lysosomal PH can prevent LDL oxidation. Given that proton pump inhibitors can decrease the intra-lysosomal acidicty through inhibition of the lysosomal membrane H+/K+ATPase, theses agents could afford protection against atherosclerosis and xanthoma formation.

A succinct review of the general and immunological pharmacologic effects of proton pump inhibitors.

Proton pump inhibitors (PPI) are a group of anti-ulcer agents. PPI have selective anti-cancer effects via apoptosis of tumour, sensitization of cancer cell to chemotherapy and radiotherapy. Also PPI have anti-malarial and anti-leishmanial activity. Rising of endosomal (P)H inhibits the presentation of antigens that enter cell through endocytosis. PPI can affect transmigration of leucocytes from vessels to inflammatory sites and also can mitigate neutrophile adherence to endothelial cell. PPI increase the intralysosomal (P)H and decrease the expression of intracellular adhesion molecules. Therefore PPI can exert immunomodulation in immunological diseases through hampering antigen processing, antigen presentation, and leucocytes transmigration.

Dramatic verrucae confined to the lower lip.

A 16-year-old boy presented with a 3-year history of development of small papules on his lower lip.

Essential type II mixed cryoglobulinemia causing pyoderma gangrenosum-like ulcers.

A 47-year-old, otherwise healthy woman presented with multiple deep ulcers located primarily on her lower extremities that presented 6 days ago as blisters. A biopsy revealed livedoid vasculopathy, without any evidence of vasculitis. Extensive laboratory workup was positive only for type II cryoglobulins.

Possible molecular mechanisms to account for the involvement of tryptase in the pathogenesis of psoriasis.

Tryptase has been suggested to take part in the pathophysiology of psoriasis mainly through the production of C3a by cleaving C3. However, studies using tryptase preparations of high purity do not support this notion. Therefore, although tryptase is unanimously believed to be involved in the immunopathogenesis of psoriasis, no convincing mechanism has been proposed for its role. This paper proposes several mechanisms by which this enyme may exert its role in the pathobiology of psoriasis. Tryptase is a mitogen for epithelial cells and stimulates IL-8 production and ICAM-1 expression by these cells. It also induces the expression of mRNA for IL-1beta and IL-8 and stimulates the selective release of IL-8 from endothelial cells and TNF-alpha, IL-1beta, and IL-6 from lymphocytes and monocytes. Besides itself being a chemoattractant for neutrophils, tryptase activates mast cells and generates kinins from kininogen, thereby playing a crucial role in leukocyte infiltration into psoriatic lesions. This enzyme also induces leukocyte infiltration partly through activating endothelial PAR-2, which contributes to leukocyte rolling, adherence and recruitment by inducing the release of endothelial platelet-activating factor. Through activating PAR-2, tryptase could also trigger the development of Langerhans cells which play a crucial role in the pathophysiology of psoriasis. This enzyme is a mitogen for fibroblasts, which are probably involved in the pathophysiology of psoriasis through production of insulin-like growth factor-I (IGF-I). Tryptase is a gelatinase and also activates stromelysin-1 (MMP-3), thereby contributing to the disruption of psoriatic basement membrane and to the joint damage seen in psoriatic arthritis. Increase of tryptase levels following trauma could also provide a mechanism for Koebner phenomenon seen in psoriasis.

Pyridoxal 5'-phosphate as a novel weapon against autoimmunity and transplant rejection.

Activation of CD4 T cells by antigen-presenting cells is required for the full expression of most autoimmune diseases and allogeneic transplant rejection. The extracellular part of CD4 molecule is composed of four domains, D1-D4. CD4 binds to MHC class II via its D1 and D2 domains. Pyridoxal 5'-phosphate (PLP) binds very tightly to the D1 domain of CD4 and therefore could interfere with proper CD4-MHC II interaction. Nonincorporation of CD4 into the activation complex can result in T cell apoptosis and anergy to autoantigen (s). Occupancy of D1 by PLP may prevent the proper protein-protein interactions of the CD4 molecule itself, which are important in T cell activation. PLP may also interfere with the dimerization of CD4 molecules, which occurs during T cell activation, or with the interaction of this dimer with other molecules on the T cell surface, such as CD45, thereby further rendering T cells anergic or driven to apoptosis. Therefore, PLP may have utility in the treatment of autoimmunity and transplant rejection. Furthermore, as the interaction of the HIV gp120 and CD4 occurs via D1, PLP is supposed to have anti-HIV effect as well. PLP may prove of special utility in the treatment of patients affected with both autoimmunity and HIV, for whom the routine immunosuppressives are contraindicated.

Tranilast: a novel weapon against insulin resistance.

Oxidative stress and inflammatory cytokines such as monocyte chemoattractant protein 1 (MCP-1), TGF-beta, and IL-2 are supposed to play crucial roles in the pathogenesis of insulin resistance (IR). Tranilast is an anti-allergic drug which exerts anti-inflammatory and anti-angiogenesis effects through inhibition of expression of MCP-1, TGF-beta, and antigen-induced IL-2 lymphocyte responsiveness. It also possesses a certain antioxidant activity. Considering the above facts and in view of its safety, tranilast may prove invaluable in the treatment of IR.