A liver fibrosis cocktail? Psoriasis, methotrexate and genetic hemochromatosis

BACKGROUND: Pathologists are often faced with the dilemma of whether to recommend continuation of methotrexate therapy for psoriasis within the context of an existing pro-fibrogenic risk factor, in this instance, patients with genetic hemochromatosis. CASE PRESENTATIONS: We describe our experience with two male psoriatic patients (A and B) on long term methotrexate therapy (cumulative dose A = 1.56 gms and B = 7.88 gms) with hetero- (A) and homozygous (B) genetic hemochromatosis. These patients liver function were monitored with routine biochemical profiling; apart from mild perivenular fibrosis in one patient (B), significant liver fibrosis was not identified in either patient with multiple interval percutaneous liver biopsies; in the latter instance this patient (B) had an additional risk factor of partiality to alcohol. CONCLUSION: We conclude that methotrexate therapy is relatively safe in patients with genetic hemochromatosis, with no other risk factor, but caution that the risk of fibrosis be monitored, preferably by non-invasive techniques, or by liver biopsy

UVA/UVA1 phototherapy and PUVA photochemotherapy in connective tissue diseases and related disorders: a research based review

BACKGROUND: Broad-band UVA, long-wave UVA1 and PUVA treatment have been described as an alternative/adjunct therapeutic option in a number of inflammatory and malignant skin diseases. Nevertheless, controlled studies investigating the efficacy of UVA irradiation in connective tissue diseases and related disorders are rare. METHODS: Searching the PubMed database the current article systematically reviews established and innovative therapeutic approaches of broad-band UVA irradiation, UVA1 phototherapy and PUVA photochemotherapy in a variety of different connective tissue disorders. RESULTS: Potential pathways include immunomodulation of inflammation, induction of collagenases and initiation of apoptosis. Even though holding the risk of carcinogenesis, photoaging or UV-induced exacerbation, UVA phototherapy seems to exhibit a tolerable risk/benefit ratio at least in systemic sclerosis, localized scleroderma, extragenital lichen sclerosus et atrophicus, sclerodermoid graft-versus-host disease, lupus erythematosus and a number of sclerotic rarities. CONCLUSIONS: Based on the data retrieved from the literature, therapeutic UVA exposure seems to be effective in connective tissue diseases and related disorders. However, more controlled investigations are needed in order to establish a clear-cut catalogue of indications

Chemically induced hair loss/alopecia

Increased shedding of hair and noticeable hair thinning or baldness (alopecia) are increasingly cited as side effects of exogenous chemicals/drugs. This chapter reviews some drugs implicated as well as mechanisms that may be responsible, describes criteria for defining the mechanism, and proposes animal and human assay models. This background provides the basis of similar judgment as relates to percutaneous penetration (and inhalation) of chemicals at the work site. Hair anatomy: Hair represents complete maturation of follicular matrical cells and is a fully cornified structure that emanates from a follicle and extends above the surface of the skin from varying distances. It has three components: an outer cuticle, a cortex, and an inner medulla. Hair grows in three phases: (1) growing or anagen, (2) involution or catagen, and (3) resting or telogen. Nonchemical-related hair loss: Few endogenous events affecting hair growth are delineated. Extreme starvation or protein deprivation may result in formation of sparse or brittle hair through diminished mitotic activity. Also major systemic insult, such as high fever, major surgery, illness, or trauma may result in hair follicles being thrown into an untimely telogen effluvium. Anagen versus telogen hair loss: Chemicals or medications may either cause excessive hair shedding by precipitating telogen development, directly poison the anagen root, or work in other undetermined ways. The phase of hair loss may be determined by examining the shed or easily plucked hair. Proving that alopecia in an individual is caused by a chemical/drug may be difficult; the most conclusive demonstration of chemical-/drug-related hair loss is reproduction of hair loss with repeated administration of the putative materials. However, the pathobiology of the response of the human hair follicle to chemotherapy is largely unknown. Hair loss is discussed in detail. Among the subjects of discussion are types of hair loss (e.g., anagen, medications precipitating telogen), chemicals causing hair loss (e.g., antimitotic agents, phenyl glycidyl ether), medications causing hair loss of unknown type (e.g., antithyroid drugs), medications possibly associated with hair loss, as well as chemically induced cosmetic alopecia, and typical scenarios in alleged occupational hair loss