Faculty Bibliography

Cutaneous photosensitivity in a 43-year-old man with idiopathic sideroblastic anemia associated with an abnormal porphyrin profile is reported. This condition was associated with elevated free erythrocyte porphyrin, plasma protoporphyrin, urine porphyrins (predominantly coproporphyrin), stool porphyrins (predominantly protoporphyrin), decreased ferrochelatase activity, and deletion of portions of the long arms of chromosomes 18 and 20. Five other patients with sideroblastic anemia and abnormal porphyrin profiles have been described; all but one of these patients had photosensitivity. The porphyrin profile of this patient is similar to that of three other previously described patients

BACKGROUND AND DESIGN--Cutaneous T-cell lymphoma (CTCL) is a slowly advancing disease that initially presents in the skin and may later progress to involve the lymph nodes and viscera. Since CTCL most often presents on non-sunlight-exposed regions of the body, a possible protective role for UVB irradiation has been suggested. Recent observations have also found that UVB irradiation serves an immunoregulatory role. Given that limited data are available regarding the use of UVB phototherapy in treating CTCL, a retrospective nonrandomized study of 37 nonconsecutive patients with early CTCL was performed to assess the efficacy of UVB phototherapy in the treatment of CTCL. RESULTS--Twenty-five (71%) of the 35 patients treated with UVB phototherapy (two were unavailable for follow-up) achieved a total clinical remission. Median time to remission was 5 months, and median duration of the remission was 22 months. Twenty-five (83%) of 30 patients with disease limited to patches achieved remission, whereas none of the patients with plaque-level disease achieved a remission. Of the 25 patients who achieved complete remission, five (20%) had a recurrence of CTCL. CONCLUSIONS--Phototherapy with UVB appears to be effective in patients with early patch-stage CTCL

Adjunctive topical corticosteroids are often administered with UV-B phototherapy or oral psoralen plus UV-A (PUVA) photochemotherapy for the treatment of psoriasis. Five studies comparing PUVA alone with PUVA and topical corticosteroid preparations showed more rapid rates of clearing and a smaller total UV-A exposure with the latter regimen. However, one study demonstrated a higher relapse rate in association with corticosteroid use. Further studies to better define these risks are recommended. Six of seven reports evaluating the use of topical corticosteroid preparations with UV-B phototherapy failed to demonstrate an advantage to this regimen when compared with UV-B phototherapy alone. Therefore, the use of a topical corticosteroid preparation with UV-B phototherapy for the treatment of psoriasis is not recommended

To evaluate further the interactions of C5a and mast cells in cutaneous inflammation, the ability of human native C5a (nC5a) (10 to 500 ng/ml) and human recombinant C5a (rC5a) (10 ng/ml to 100 ng/ml) to induce histamine release from purified BALB/c cutaneous mast cells (CMC) and peritoneal mast cells (PMC) was analyzed. It was found that nC5a induced histamine release from CMC but not from PMC, with a maximal net release at 250 ng/ml nC5a (22.8 +/- 2.6%). Kinetic experiments demonstrated that nC5a-induced maximal net histamine release occurred 5 min after the presentation of this stimulus (25.8 +/- 6.0%). Using rC5a and CMC, dose-response studies indicated a maximal net release of 7.0 +/- 1.7% at rC5a of 10 ng/ml, and kinetic studies showed a maximal net release at 5 min of incubation (12.9 +/- 1.6%). Release induced by rC5a was calcium-dependent, and peaked at 30 degrees C. These results indicate that functional heterogeneity exists between the CMC and the PMC of BALB/c mice, that C5a is a relevant stimulus for characterization of this heterogeneity, and that CMC from these animals can serve as a convenient in vitro model for the study of human C5a-mast cell interactions. In vivo, injections of nC5a (25-100 ng) and rC5a (25-100 ng) into the skin of BALB/c mice induced an increase in cutaneous vasopermeability, as assessed by the extravasation of intravenously injected 125I-bovine serum albumin. nC5a induced a dose-dependent increase in vasopermeability, whereas alterations induced by rC5a plateaued at 50 ng. The C5a-induced vasopermeability was markedly enhanced in animals that had been previously treated with an inhibitor of serum carboxypeptidase, which converts C5a to the less potent derivative, C5a des Arg. These findings suggest that carboxypeptidase plays an important role in vivo in the modulation of C5a-induced cutaneous inflammation in murine skin

Urticaria and angioedema are clinical manifestations of various immunologic and inflammatory mechanisms, or they may be idiopathic. The respiratory and gastrointestinal tracts as well as the cardiovascular system may be involved in any combination. Patients with urticaria and/or angioedema can be classified based on pathophysiologic mechanisms into those with IgE-dependent or complement-mediated immunologic disorders, those with nonimmunologic disorders in which there is a direct effect on the mast cell or on arachidonic acid metabolism, and those whose condition is idiopathic. Evaluation of patients should focus on a thorough history. Laboratory tests provide minimal additional information. About one half of patients with urticaria alone and 25% with urticaria and angioedema or angioedema alone are free of lesions within 1 year. With urticaria, angioedema, or both, 20% of patients experience episodes for more than 20 years

H1-type antihistamines are considered the therapeutic agents of choice for treating urticaria and angioedema. The use of traditional H1 antihistamines is limited by their side effects. In recent years low-sedating H1 antihistamines with reduced sedative and anticholinergic side effects have become popular choices for the treatment of urticaria and angioedema. Terfenadine and astemizole are currently available in the United States, and cetirizine and loratadine, currently under review at the Food and Drug Administration, are available in other countries. Terfenadine, cetirizine, and loratadine achieve rapid peak plasma concentrations in 1 to 2 hours, whereas astemizole has a slow onset of action. In double-blind, placebo-controlled studies of chronic idiopathic urticaria, low-sedating H1 antihistamines were more effective than placebo. The choice of a particular low-sedating H1 antihistamine depends on pharmacokinetic considerations and frequency of administration

The most frequent site of organ involvement in patients with any form of mastocytosis is the skin. Cutaneous expressions include urticaria pigmentosa, mastocytoma, diffuse and erythrodermic cutaneous mastocytosis, and telangiectasia macularis eruptiva perstans. The cutaneous lesions tend to appear early in life. Although urticaria pigmentosa has been reported in 12 pairs of twins and one set of triplets, the majority of affected individuals have no familial association. Most patients with systemic mastocytosis have skin lesions; however, an occasional patient will have systemic disease with no other skin features than flushing. In lesional cutaneous sites and in non-lesional skin, there is an increase in the number of mast cells. Electron microscopy shows quantitative differences between lesional skin mast cells from patients with and without systemic disease. The mast cells from adult patients with systemic disease have a larger mean cytoplasmic area, nuclear size, and granule diameter. The granules contain predominantly grating/lattice structures. The cutaneous mast cells contain tryptase and chymase. They retain their functional reactivities to relevant secretory stimuli, such as C3a, morphine sulfate, and calcium ionophore A23187. Lesional skin contains histamine, leukotriene B4, prostaglandin D2, 5-hydroxyeicosatetraenoic acid, platelet-activating factor, and heparin. Treatment of the cutaneous manifestations includes the use of H1 and H2 antihistamines, oral disodium cromoglycate, psoralens plus ultraviolet A photochemotherapy, and potent topical corticosteroid preparations.Journal of Investigative Dermatology (1991) 96, 32S-39S; doi:10.1111/1523-1747.ep12468973