Antonio Tulli

Vitiligo associated with other autoimmune diseases: polyglandular autoimmune syndrome types 3B + C and 4

Vitiligo is a common skin disease characterized by depigmented maculae resulting from a reduction of the number and function of melanocytes. Many studies suggest that vitiligo might be an autoimmune disease. Vitiligo has been frequently described in association with other autoimmune diseases. Among the diseases described in association with vitiligo are the so‐called autoimmune polyglandular syndromes (APS). Vitiligo can be present in all types of APS but the most frequent association appears to be in APS‐3. APS‐3 was defined as the association between autoimmune thyroiditis and another autoimmune disease. Here we report one patient with thyroiditis, vitiligo and autoimmune gastritis (APS‐3B + C), one patient with chronic autoimmune thyroiditis, vitiligo and alopecia (APS‐3C), and one case of a young patient with type 1 diabetes mellitus and vitiligo (APS‐4), according to the newest classification. We stress the importance of a thorough assessment for autoimmune diseases in selected patients with vitiligo.

Polyglandular autoimmune diseases in a dermatological clinical setting: vitiligo-associated autoimmune diseases.

Vitiligo is an acquired hypomelanotic disorder characterized by depigmented macules resulting from the loss of functional melanocytes. Many different etiological hypotheses have been suggested for vitiligo, the most recent of which involves a combination of interacting environmental and genetic factors. Among the various pieces of evidence in support of an autoimmune origin of vitiligo, there is the epidemiological association with several autoimmune diseases. The most frequently reported association is with autoimmune thyroiditis; however, other diseases such as rheumatoid arthritis, diabetes mellitus, pernicious anemia and chronic urticaria have been described in variable percentages, depending upon the genetics of the population studied. Among the diseases described in association with vitiligo there are the so-called autoimmune polyglandular syndromes (APS). Here we report 31 cases of APS diagnosed in 113 vitiligo patients, according to the newest classification. Autoimmune association was more present in generalized non segmental vitiligo and was more frequent in females. The most frequent association was with thyroid autoimmune disease, followed by autoimmune gastritis and alopecia areata. ANA positivity was similar to that reported previously in the general population. We stress the importance of an assessment for autoimmune diseases in vitiligo patients.

Interferon β-1b modulates MCP-1 expression and production in relapsing–remitting multiple sclerosis

Monocyte chemoattractant protein-1 (MCP-1) seems to be involved in the pathogenesis of multiple sclerosis (MS). We found that in unstimulated (PHA ) and PHA-stimulated (PHA + ) peripheral blood mononuclear cells (PBMC), MCP-1 and TNFa levels are higher in stable untreated MS patients. Interferon gamma (IFNg) is higher in relapsing patients in PHA cultures and in stable patients in PHA + cultures. Chronic IFNb-1b treatment down-regulates TNFa, IFNg and MCP-1 production except for TNFa in relapsing patients. IFNb-1b, in vitro, increases MCP-1, TNFa and IFNg spontaneous production in all patients. Multivariate analysis suggests that MCP-1 production is dependent from clinical status and not from TNFa and IFNg production. Logistic regression analysis shows that MCP-1 production is significantly modified by treatment. Further studies are needed to clarify the role of MCP-1 in MS. D 2002 Elsevier Science B.V. All rights reserved.

Elevated 8-isoprostane levels in basal cell carcinoma and in UVA irradiated skin.

Isoprostanes are prostaglandin isomers produced from the peroxidation of polyunsaturated fatty acids from the cellular membrane. They have been used as a specific index of cellular lipoperoxidation and as an indirect measure of oxidative stress. However, these molecules also present several biological activities. An oxidative environment measured as the presence of other indirect measurements of reactive oxygen species lipoperoxidation has recently been described in basal cell carcinoma, the most frequent type of non-melanoma skin cancer. This study aims to measure the levels of 8-isoprostaglandin F2α, an isoprostane widely studied in other models as a by-product of ROS-induced lipid peroxidation, in basal cell carcinoma and in UVA irradiated healthy skin. We found that 8-iso-PGF2α is present in higher levels in BCC specimens compared to healthy non sun-exposed skin, confirming previous studies on the production of lipoperoxidation in this tumor. Moreover, we demonstrated that topical pre-treatment with a compound containing vitamin E is capable of reducing 8-iso-PGF2α formation in UV irradiated skin suggesting a role for isoprostanes in UV induced inflammation and eventually carcinogenesis and confirming the function of vitamin E as an antioxidant in this model.

Treatment of Cutaneous Calciphylaxis with Sodium Thiosulfate

Cutaneous calciphylaxis is a potentially fatal condition characterized by calcium deposition in dermal arterioles and the subsequent development of livedo reticularis, plaques, and extremely painful ulcers. This condition may be present in up to 4% of end-stage renal disease patients. Several treatments, which mainly attempt to control calcium phosphate metabolism, are available for this condition.We describe two patients treated with sodium thiosulfate with good results. Moreover, we also performed a PubMed literature search of sodium thiosulfate treatment for calciphylaxis. We found 41 cases of which most (>90%) presented a rapid and sustained resolution, indicating this drug is a very good candidate for the treatment of this condition.

Lupus vulgaris developing at the site of misdiagnosed scrofuloderma.

Cutaneous tuberculosis is a rare form of extrapulmonary tuberculosis primarily occurring in developing countries. The recent increase in the incidence of tuberculosis, especially due to human immunodeficiency virus (HIV) infections, has led to a resurgence of extrapulmonary forms of this disease. We describe a case of lupus vulgaris in a 33‐year‐old woman who had a 5‐year history of a slowly growing plaque on her neck. The lesion was located at the site of surgery repairing the scar resulting from the incision of a subcutaneous abscess during childhood. This lesion was misdiagnosed as bacterial abscess. Histopathologic examination of the plaque revealed non‐caseating tuberculoid granulomas consisting of lymphocytes, epithelioid and giant cells. Staining for acid‐fast bacilli and culture from biopsied tissue was negative. Polymerase chain reaction (PCR) for detection of Mycobacterium tuberculosis DNA, performed on a skin biopsy specimen, was positive. A diagnosis of lupus vulgaris developing at the site of a previous misdiagnosed scrofuloderma was made. Conventional antitubercular therapy with rifampicin, isoniazid and ethambutol was administered for 6 months, resulting in resolution of the lesion.

Tannic acid induces in vitro acantholysis of keratinocytes via IL-1alpha and TNF-alpha.

The mechanism of acantholysis in pemphigus vulgaris (PV) is an intriguing argument since several chemical mediators are implicated. We previously reported a central role for IL-1α and TNF-α, both able to regulate complement activation and plasminogen activators. Very little is known about what triggers the disease (drugs, viruses or food). In this study, we evaluate the molecular role of tannins in acantholysis. By HPLC chromatography we measured tannic acid (TA) and gallic acid (GA) in blister fluid of 4 groups of patients divided according to their dietary habits, including a regular diet, a diet rich in tannins, a diet free of tannins, and a group of pemphigus patients. Blister fluid was obtained from patients using a suction blister apparatus. We show that people with a diet rich in tannins have increased tannin metabolites (TA and GA) in the skin in respect to controls (tannin-rich diet: GA = 194.52±2.39 nmol/ml; TA = 348.28±1.4 nmol/ml versus tannin-Mediterranean diet: GA = 15.28±1.63 nmol/ml; TA = 22.81±1.68 nmol/ml). PV patients showed similar values to the Mediterranean diet population (PV patients: GA = 95.8±1.97 nmol/ml; TA = 199.09±4.15 nmol/ml versus Mediterranean diet: GA = 83.53±2.35 nmol/ml; TA = 195.1±2.50 nmol/ml). In an in vitro acantholysis system using TA and PV-IgG we show that TA 0.1 mM in NHEK culture is able to induce acantholysis. This effect was able to amplify the acantholytic action of PV-IgG in vitro. A blocking study using anti IL-1α and anti TNF-α antibodies showed a reduction in TA-induced acantholysis. Taken together, these results suggest that a diet rich in tannins could be a trigger in genetically predisposed patients. If these data are confirmed, a complementary diet poor in tannins may be useful in patients affected by PV.

TNFalpha and its receptors in psoriatic skin, before and after treatment with etanercept.

Psoriasis is a chronic inflammatory skin condition characterized by inflammatory dermal infiltrate and hyperproliferative keratinocytes. The pathogenesis of this disease is mediated by a dysregulation of the innate immunity and cytokine production. Tumor Necrosis Factor alpha (TNFα) is considered the most important cytokine involved in the pathological mechanism of psoriasis. Recently, several therapies have been introduced for the treatment of psoriasis that try to block TNF alpha activity. Among these treatments Etanercept is a fusion protein that specifically targets TNF alpha. We performed a study on twelve psoriatic patients aimed at evaluating the effect of Etanercept treatment on the production and expression of TNFα and its receptors, in lesional and uninvolved psoriatic skin. We demonstrated that after three month of Etanercept treatment at 50 mg/wk, TNF, TNF-RI and TNF-RII immunostaining in lesional and non-lesional skin samples of patients was greatly reduced, suggesting that this treatment not only acts on stable lesional plaques, but also at a very early stage of the disease.

Finger Thermoregulatory Model Assessing Functional Impairment in Raynaud’s Phenomenon

Raynaud’s Phenomenon (RP) is a paroxysmal vasospastic disorder of small arteries, pre-capillary arteries, and cutaneous arteriovenous shunts of the extremities, typically induced by cold exposure and emotional stress. RP is either primary (PRP) or secondary to systemic sclerosis. In this study we use Control System Theory to model finger thermoregulatory processes in response to a standardized cold challenge (a diagnostic test routinely performed for differential diagnosis of RP). The proposed model is based on a homeostatic negative feedback loop, characterized by five distinct parameters which describe how the control mechanisms are activated and maintained. Thermal infrared imaging data from 14 systemic sclerosis subjects (SSc), 14 PRP, and 16 healthy control subjects (HCS) were processed. HCS presented the fastest active recovery, with the highest gain. PRP presented the slowest and weakest recovery, mostly due to passive heat exchange with the environment. SSc presented an intermediate behavior, with the longest delay of response onset. The estimated model parameters elucidated the level of functional impairment expressed in the various forms of this disease.

Topical cyclosporin in the treatment of dermatologic diseases.

In spite of the drugs toxicity, cyclosporine A (CsA) is largely used in several diseases, including dermatological pathologies, with beneficial results. In dermatology cyclosporin-A reduces the severity of psoriasis symptoms, Bechets disease, pyoderma gangrenosum, blistering disorders, aftous stomatitis, lichen planus, atopic dermatitis, alopecia and allergic contact dermatitis.