A. Parodi

Flushing in rosacea: A possible mechanism

SummaryFlushing in rosacea has been investigated by means of (a) pharmacological inhibition of some possible chemical mediators and (b) titration of bradykinin as a possible effector directly in the blood. Clonidine-inhibited flushing was seen in all patients (mean 45%), other drugs had poorer results. Bradykinin increased in all patients at the climax of flushing (mean 60%). These findings support the hypothesis that epinephrine promotes a bradykinin release responsible for vasodilation.ZusammenfassungDie Flush-Reaktion bei Rosazea wurde (a) durch pharmakologische Hemmung einiger Mediatoren und (b) durch Titration von Bradykinin, das möglicherweise einen direkten Effektor im Blut darstellt, untersucht.Clonidin konnte die Flush-Reaktion bei allen Patienten (durchschnittlich um 45%) hemmen. Andere Medikamente zeigten schlechtere Ergebnisse. Der Bradykininspiegel fand sich auf dem Höhepunkt der Flush-Reaktion bei allen Patienten deutlich eleviert (durchschnittlich um 60%). Diese Ergebnisse belegen die Hypothese, daß Adrenalin die Freisetzung von Bradykinin fördert und somit eine Vasodilatation bewirken kann.

HLA‐DQB1 alleles in Italian patients with mucous membrane pemphigoid predominantly affecting the oral cavity

Background Mucous membrane pemphigoid (MMP) used to be considered as a single entity but it is now evident that a range of variants exists. Among them, pure ocular cicatricial pemphigoid (OCP) and pure oral pemphigoid (OP) appear to be very different subsets. Previous immunogenetics studies have found increased occurrence of the DQB1*0301 allele mainly in patients with OCP whereas in patients with OP the data are more open to doubt.

Flushing in rosacea: An experimental approach

SummaryA simple method is described which causes rosacea patients to flush. This flush is experienced similarly to the flush which occurs spontaneously and its intensity can be measured and monitored wuantitatively. Therefore, it can be used as a suitable experimental tool to measure and compare the inhibitory effects of some drugs, as well as the fluctuations of the blood level of certain chemical vasoactive mediators.ZusammenfassungEs wird eine einfache Methode zur Erzeugung des Flushsyndroms beim Rosaceakranken beschrieben. Dieser Flush ist dem spontanen Flush ähnlich. Seine Intensität kann durch Erfassung der Hauttemperatur gemessen werden. Diese Methode ist dazu geeignet, um die Inhibitionswirkungen einiger Arzneien und vasoaktiver Substanzen zu studieren und zu vergleichen.

Frequency of IgA antibodies in pemphigus, bullous pemphigoid and mucous membrane pemphigoid.

Circulating and bound IgA antibodies can be found in the autoimmune blistering diseases, but their prevalence, clinical relevance and target antigens remain unknown. Thirty-two patients with pemphigus, 73 with bullous pemphigoid and 28 with mucous membrane pemphigoid were studied retrospectively. Direct immunofluorescence (DIF) analysis of IgG, IgA, IgM and C3 was carried out for all cases. Sera were studied by standard indirect immunofluorescence, indirect immunofluorescence on salt-split skin, immunoblotting for bullous pemphigoid and mucous membrane pemphigoid and ELISA for pemphigus. With DIF, we found IgA autoantibodies in 22 of all 133 cases. Circulating IgA antibodies to skin were detected in 2 of 3 IgA-DIF-positive patients with pemphigus, in 3 of 6 with bullous pemphigoid, and in 6 of 13 with mucous membrane pemphigoid. We confirm that the IgA reactivity is more frequently associated with mucous membrane involvement, especially in cases without critical involvement (5/8). The role of IgA and its antigenic specificity in these diseases remain unclear.

Gene Expression Profiling in Dermatitis Herpetiformis Skin Lesions

Dermatitis herpetiformis (DH) is an autoimmune blistering skin disease associated with gluten-sensitive enteropathy (CD). In order to investigate the pathogenesis of skin lesions at molecular level, we analysed the gene expression profiles in skin biopsies from 6 CD patients with DH and 6 healthy controls using Affymetrix HG-U133A 2.0 arrays. 486 genes were differentially expressed in DH skin compared to normal skin: 225 were upregulated and 261 were downregulated. Consistently with the autoimmune origin of DH, functional classification of the differentially expressed genes (DEGs) indicates a B- and T-cell immune response (LAG3, TRAF5, DPP4, and NT5E). In addition, gene modulation provides evidence for a local inflammatory response (IL8, PTGFR, FSTL1, IFI16, BDKRD2, and NAMPT) with concomitant leukocyte recruitment (CCL5, ENPP2), endothelial cell activation, and neutrophil extravasation (SELL, SELE). DEGs also indicate overproduction of matrix proteases (MMP9, ADAM9, and ADAM19) and proteolytic enzymes (CTSG, ELA2, CPA3, TPSB2, and CMA1) that may contribute to epidermal splitting and blister formation. Finally, we observed modulation of genes involved in cell growth inhibition (CGREF1, PA2G4, and PPP2R1B), increased apoptosis (FAS, TNFSF10, and BASP1), and reduced adhesion at the dermal epidermal junction (PLEC1, ITGB4, and LAMA5). In conclusion, our results identify genes that are involved in the pathogenesis of DH skin lesions.

Follicular Impetigo as Presenting Sign of Systemic Lupus erythematosus

A patient with an unusual form of follicular impetigo, who later developed classical systemic lupus erythematosus (SLE) is described. When she had pyoderma, direct immunofluorescence and serology already suggested a connective tissue disease. Pyoderma could have been the presenting manifestation of SLE.

Generalized bullous morphoea. Efficacy of salazopyrin.

Although 532 nm laser light was able to induce a brownish colouration in five patients, this was slight, transient and of no cosmetic value to the patient, Hyperpigmentation in normal perilesional skin in contrast occurred markedly and was more persistent. In conclusion, within the parameters used in this study, Nd/YAG laser irradiation was ineffectual in inducing permanent repigmentation in vitiliginous skin despite experimental evidence of the ability of this laser to increase melanogenesis. References

Fosinopril as a Possible Pemphigus-Inducing Drug

Fosinopril has recently been added to the angiotensin-converting enzyme inhibitors inducing pemphigus. The observation of a patient in whom pemphigus vulgaris (PV) worsened after taking fosinopril prompted us to study an experimental way to assess its responsibility. Slices of normal human skin (NHS) were simultaneously incubated for 2, 6, 12 and 24 h at 4°C with progressively diluted fosinopril and captopril solutions and used as indirect immunofluorescence (IIF) substrates for 2 sera containing anti-desmoglein-3 (anti-Dsg3) antibodies at a dilution of 1/160. With captopril, IIF was negative, irrespective of dilution and time of incubation. Only at 1/40,000 dilution was IIF positive. With fosinopril, IIF was negative for the 2- and 6-hour-long incubations but turned positive after 12 h and so remained with all other solutions and incubation times. IIF negativity with captopril suggests that anti-Dsg3 antibodies contained in the PV sera were unable to find molecules in NHS to bind to. Captopril would therefore induce acantholysis by blocking the adhesion molecules. With fosinopril, instead, a partial block of the adhesion molecules was seen only with the very concentrated solution, unlikely to occur in vivo. Fosinopril, therefore, is probably unable to block the adhesion molecules in vivo. Our method might be used to verify the acantholytic properties of a drug.

Generalized annular granuloma associated with crowned dens syndrome, which resolved with colchicine treatment

Granuloma annulare (GA) is a chronic, benign, and usually self‐limiting cutaneous inflammatory disease, typically characterized by small, localized, skin‐coloured papules that are usually asymptomatic or mildly pruriginous. Its aetiopathogenesis is still unknown and treatments are rarely effective. Generally, 50–70% of localized GA cases are self‐limiting and show spontaneous resolution after 1–2 years, whereas disseminated GA is less likely to disappear without treatment. Treatment of generalized GA is usually based on single case reports, and only a few studies involving large case series have been published. We present the case of a patient affected by generalized GA, which resolved after colchicine treatment used for concomitant crowned dens syndrome due to calcium pyrophosphate deposition disease (CPPD). Colchicine may have worked by a direct action on GA or, alternatively, by controlling CPPD, as a possible trigger. As the low‐dosage colchicine treatment was well tolerated by our patient, this could be easily used in the management of GA. However, further studies are needed to confirm the action of colchicine on GA.

Hepatitis C virus-related cutaneous vasculitis in the absence of specific antibodies.

1 Anderson CK, Mowad CM, Goff ME, Pelle MT. Bullous pemphigoid arising in surgical wounds. Br J Dermatol 2001; 145: 670–2. 2 Wojnarowska F, Eady RA, Burge SM et al. Bullous eruptions. In: Champion RH, Burton JL, Burns DA, Breathnach SM, eds. Textbook of Dermatology, Rook ⁄ Wilkinson ⁄ Ebling, 6th edn. Oxford: Blackwell Science 1998, 1866– 77. 3 Panayiotou BN, Prasad MV, Zaman MN. Frusemide induced bullous pemphigoid. Br J Clin Pract 1997; 51: 49–50. 4 Ghura HS, Johnstone GA, Milligan A. Development of bullous pemphigoid after split skin grafting. Br J Plastic Surg 2001; 54: 447–9. 5 McGrath J, Black M. Split skin grafting and bullous pemphigoid. Clin Exp Dermatol 1991; 16: 72–3.