N. Mozzanica

Effectiveness of cyclosporine treatment in severe psoriasis: A clinical and immunologic study

The effectiveness of low doses of cyclosporine (3 to 5 mg/kg/day) for short-term treatment in 13 patients with severe psoriasis was studied. The psoriasis cleared in 12 of 13 patients within 3 to 4 weeks of treatment, and there was appreciable improvement in the thirteenth patient. No major side effects were observed: two patients showed biochemical evidence of slight transient renal dysfunction and three others had cutaneous infections (two viral and one mycotic). An immunohistologic study showed that the psoriatic plaques contained an infiltrate composed mainly of activated helper T lymphocytes. After 15 days of cyclosporine treatment, CD4+ cells were significantly fewer in the epidermis and dermis, and Langerhans cells were more regularly distributed in the epidermis. Our studies of neutrophil chemotaxis showed that it is not significantly influenced by cyclosporine in vitro but is decreased in vivo.

Contact and photocontact allergy to ketoprofen: clinical and experimental study

In the last 3 years, we have studied 10 patients with allergic reactions to topical ketoprofen. We have investigated the sensitization and irritant potential of the drug and the possibility of cross‐reactivity with other aryl‐propionic non‐steroidal anti‐inflammatory drugs (ibuproxam, ibuprofen, naproxen, fenoprofen, flubiprofen and tiaprofenic acid), 2 of our patients had contact dermatitis, and the other 8 photocontact dermatitis. One of our patients showed cross‐reactivity between ketoprofen and ibuproxam on patch testing. In the photopatch tests, we observed cross‐reactivity between ketoprofen and tiaprofenic acid in 2 patients, and cross‐reaction between ketoprofen and ibuproxam and flurbiprofen in another case. Experimental studies, including human maximization and photomaximization tests, performed in 20 healthy volunteers, showed a complete absence of sensitization. 3 volunteers showed a marked irritant reaction to ketoprofen (20% pet.) during either maximization (2 cases) or photomaximization (I case) tests. Although ketoprofen appears not to be a sensitizing agent in human volunteers, the fact that photosensitization to this drug seems to be quite common after topical use suggests that there are some local or individual factors, at present unknown, facilitating the development of allergy.

Plasma α-melanocyte-stimulating hormone, β-endorphin, met-enkephalin, and natural killer cell activity in vitiligo

Background: The immune system is important in the pathogenesis of vitiligo, and emotional stress has precipitated vitiligo in some patients. Opioid peptides, β-endorphin, met-enkephalin, and α-melanocyte-stimulating hormone (MSH) act as immunomodulators, and their secretion increases during periods of stress. Objective: To see whether these three neuropeptides might be related to vitiligo itself or to some alterations of the immune system in patients with vitiligo, we compared circadian variations in their plasma concentrations and natural killer cell activity of peripheral blood lymphocytes in 14 patients with vitiligo with those of 12 healthy subjects. Methods: Plasma concentrations of neurohormones were evaluated by radioimmunoassay (immunoradiometric assay for β-endorphin). Natural killer cell activity (NKCA) was assayed against K562 cells by 51 Cr release technique. Data were compared by the Student t test and analyzed by cosinor analysis. Results: The NKCA in vitiligo patients was higher than in controls but had similar circadian rhythm. α-MSH had no circadian rhythm in controls or in patients; plasma α-MSH levels were the same. Daily met-enkephalin and β-endorphin oscillations in patients were no longer circadian. β-Endorphin plasma levels in stable vitiligo were higher than in controls. There were no differences between patients with active vitiligo and normal subjects. Met-enkephalin plasma levels were generally higher in vitiligo patients, especially in the one with active vitiligo, than in controls. Conclusion: In vitiligo there are aberrations in neuropeptide, β-endorphin, and met-enkephalin secretion. The plasma met-enkephalin level is positively correlated with the aggressiveness of the disease.

T cell subpopulations in vitiligo: A chronobiologic study

The circadian rhythms of helper (CD4) and suppressor (CD8) T cells from the peripheral blood of 12 vitiligo patients (seven with active disease, five with static) and 12 healthy control subjects were studied. Patients with active vitiligo had a lower percentage of CD4+ cells than did control subjects at 0000 hours and at 0600 and 1200 hours; there were no differences between these values in patients with static vitiligo and those in control subjects. The percentage of CD8+ cells were lower at 1200 and 1800 hours in both active and static vitiligo patients than in control subjects. Cosinor analysis of the CD4+ cells showed a circadian rhythm in static vitiligo, whereas the rhythmicity was lost in active vitiligo. CD8+ cells did not show any circadian rhythm in either active or static vitiligo. Our data show more striking aberrations for T cell subtypes in active vitiligo than in static vitiligo. They suggest that cell-mediated immunity may play a role in the pathogenesis of the disease.

Association between circadian rhythms of endogenous hypothalamic opioid peptides and of natural killer cell activity

To explore in man the hypothesis that natural killer cell activity and hypothalamic-hypophyseal hormones constitute a mutually coupled multioscillatory system, we analysed and compared, in 11 healthy volunteers, the circadian variations in plasma concentrations of beta-endorphin, met-enkephalin and alpha-MSH, and of natural killer activity of peripheral blood lymphocytes. Natural killer cell activity and plasma beta-endorphin levels showed a similar circadian rhythm with the peak in the morning (acrophases at 06.14 and 08.25, respectively), whereas the circadian rhythm of met-enkephalin was approximately in antiphase to the natural killer rhythm (acrophase close to 17,00 hours). Although daily variation of alpha-MSH showed greater inter-individual variability, a circadian rhythm was statistically validated. Analysis of correlation between rhythmometric parameters (mesor, amplitude, peak and nadir) of natural killer cell activity vs neuro-endocrine hormones revealed that the minimum and medium daily concentrations of beta-endorphin correlated directly with the corresponding parameters of natural killer activity, while the maximum and medium concentrations of met-enkephalin were inversely correlated with the peak and the mesor of natural killer activity. The amplitude of natural killer cell activity oscillations correlated directly with the peak, mesor and nadir concentrations of alpha-MSH. We show here that circadian rhythms of some neuroendocrine hormones of the hypothalamic-hypophyseal axis, i.e. beta-endorphin, met-enkephalin and alpha-MSH, are significantly coupled to daily oscillations of NK cell activity.

Immunohistologic evaluation of the effect of cyclosporine treatment on the lichen planus immune infiltrate.

We have investigated immunohistologically the cutaneous immune infiltrate in the lesions of five patients with severe, extensive lichen planus of recent onset before and after 15 days of oral, low-dose cyclosporine therapy (3 mg/kg/day). Before therapy, we observed an abnormal bandlike cellular infiltrate localized in the papillary dermis, composed mostly of CD3+ cells, with a prevalence of CD4+ cells. Infiltrating lymphocytes showed markers of activation (HLA-DR antigens and interleukin 2 receptor), and there were many Langerhans (CD1+) cells in the dermal infiltrate. After 15 days of cyclosporine therapy, we observed a dramatic decrease in the total number of T cells and a corresponding decrease in interleukin 2 receptor-positive activated CD25+ cells and in antigen-presenting cells (CD1+ and CD14b+). These changes were concurrent with clinical improvement. Our results are compatible with the hypothesis that the inhibition of CD4 T cells by cyclosporine might explain the drugs therapeutic action and that the interaction between antigen-presenting cells and CD4 T cells is important in the pathogenesis of lichen planus.

Circadian rhythm of natural killer cell activity in vitiligo

Ten patients with vitiligo, either in the active (six cases) or static (four cases) phase, and twelve healthy control subjects were studied with a standard cytotoxicity assay to evaluate the circadian rhythm of natural killer cell activity from peripheral blood mononuclear cells. The natural killer cell activity was measured at the zero, sixth, twelfth, and eighteenth hours of the day. The results demonstrated that patients with vitiligo had significantly higher natural killer cell activity compared with normal controls. When patients with static and active vitiligo were compared, those with the static form had increased natural killer cell activity at all times except noon, whereas those with active form had increased natural killer cell activity only at 0600 and 1800. These changes shifted the acrophase of the circadian rhythm of each group. Indeed, by cosinor analysis, both patients with vitiligo and normal controls had similar circadian rhythms, but the acrophase was shifted from 0602 in control subjects to 0435 in the ten patients with vitiligo. The acrophase in the six patients with active vitiligo was found to be closest to that of normal controls (0508). These findings indicate that natural killer cell activity abnormalities are more marked in the static rather than in the active form of vitiligo.

Intralesional alpha 2b recombinant interferon for basal cell carcinomas.

Basal cell carcinoma (BCC) is a rather common skin neoplasm, particularly in white patients. It grows slowly, has a locally malignant behavior, and metas‐tases occur only exceptionally. It is considered to be derived from pluripotential epithelial cells that can partially differentiate towards adnexal structures and sebaceous, apocrine, and sometimes eccrine glands. Prolonged exposure to the sun, a fair and freckled complexion, x‐rays, burn scars, and arsenic by mouth are all predisposing factors for basal cell epithelioma. The face and the trunk are the parts most often affected. Some patients, especially those with a fair complexion, may have dozens of BCCs at one time.

Contact and Photoallergic Dermatitis to Topical Nonsteroidal Antiinflammatory Drugs (Propionic Acid Derivatives): A Study of Eight Cases

Many new nonsteroidal antiinflammatory drugs (NSAIDs) have been introduced into topical preparations for treatment of inflammatory or posttraumatic musculoskeletal disorders. Those NSAIDs, which are propionic acid derivatives, include ibuproxam, ibuprofen, naproxen, ketoprofen, fenoprofen, indoprofen, flurbiprofen and tiaprofenic acid, all of similar use, action, and toxicity. Cases of contact dermatitis and photodermatitis are rare and have been reported only anecdotally. We have seen eight patients with contact and photocontact dermatitis due to a single compound of this group of NSAIDs. All patients underwent ordinary patch and photopatch tests with standard series and all compounds of the aryl propionic group. Five patients had contact dermatitis: four to ibuproxam and one to ketoprofen, without any cross-reactivity, in spite of the marked chemical similarity in this group of NSAIDs. One case was a photodermatitis of an allergic type to tiaprofenic acid. The other two patients, negative for contact dermatitis, showed a typical photocontact allergy to ketoprofen, without any cross-reactivity. Other reports stated that cross-reactivity may happen, but we feel that this phenomenon is rare within this group of antigens, since the immune response, whether allergic or photoallergic, seems to be highly specific. Perhaps instead of cross-reactivity it would be better to speak of a concomitant allergy following several successive applications of topical preparations, each with a different one of these compounds.

Medicament dermatitis around leg ulcers due to lack of protein C.

The spermicidallubncant of Durex Top Safe IS tecto! and has a constituents: a spermicidal agent (texafor FNI1 = 2, 4, 6 tn-1sopropyl polyethoxy-phenol), polyethylene glycol and 2 coded perfumes. The nonspermicidal lubncant of Durex Fetherlite IS sens1tol and consists of a silicone flmd (poly-tnmethyl siloxane). Sensitization to phenoxypolyethoxy ethanol (0.5% pet.) has been described by Fisher (2). It appeared that after handling the contraceptive (Durex Top Safe) and durmg mtercourse, the partner of the patient usually placed his hands on the patients body on areas corresponding with the sites of dermatitis (Fig. 1). To which exact constituent of Tecto! (texafor FN11 or perfumes) the patient was sensitized could not be established, because she refused further testing.