Alfredo Rebora

Purpura of the ears: a distinctive vasculopathy with circulating autoantibodies complicating long‐term treatment with levamisole in children

The cutaneous side‐effects of levamisole include non‐specific and lichenoid eruptions, fixed drug eruption and, very rarely, cutaneous vasculitis. We describe a distinctive clinical and histological vasculopathy with immunological abnormalities in children with paediatric nephrotic syndrome receiving long‐term levamisole treatment. Four boys and one girl were identified. Their average age was 10 years. Levamisole had been used for an average of 24 months. Purpura of the ears was the most common finding corresponding histologically to a vasculopathic reaction pattern ranging from a leucocytoclastic and thrombotic vasculitis to a vascular occlusive disease without true vasculitis but with associated antinuclear, antiphospholipid and anticytoplasmic antibodies. The eruption resolved in all patients 2–3 weeks after the discontinuation of levamisole, but serum autoantibodies persisted for 2–14 months.

Cutaneous reactive angiomatoses: patterns and classification of reactive vascular proliferation

New and relatively old types of vascular (capillary) proliferations in the skin have been described or better categorized in the last few years. They include reactive angioendotheliomatosis, acroangiodermatitis (pseudo-Kaposi sarcoma), diffuse dermal angiomatosis, intravascular histocytosis, glomeruloid angioendotheliomatosis, and angiopericytomatosis (angiomatosis with cryoproteins). Clinically, all of them present with multiple, erythematous-violaceous and purpuric patches and plaques, sometimes evolving toward necrosis and ulceration with a wide distribution but a propensity to involve limbs. Histologically, they are characterized by different patterns of intravascular or extravascular lobular or diffuse hyperplasia of endothelial cells, pericytes, and sometimes histiocytes. Although these angioproliferations can histologically mimic vascular tumors, they are reactive in that they seem to originate from the occlusion of vascular lumina by different localized or systemic disorders and the vascular proliferation stops after the inducing hypoxic stimulus has been withdrawn. In this article, the authors review all these forms of reactive angioproliferations in the skin, suggest a novel title, cutaneous reactive angiomatoses, and propose a unifying pathogenetic mechanism.

The Management of Rosacea

Rosacea is a multiphasic disease which is associated with flushing, erythrosis, papulopustular rosacea and phymas; each phase is likely to have its own treatment. Flushing is better prevented rather than treated, and its etiology investigated. ß-Blockers, atenolol in particular, are worthy of prophylactic trials examining their efficacy in treating the flushing associated with rosacea. Currently, clonidine is the only drug available for the treatment of flushing.Treatment for erythrosis includes topical and systemic therapies. Metronidazole 1% cream and azelaic acid 20% cream have been reported to reduce the severity score of erythema. The systemic treatment of erythrosis is based on the association of Helicobacter pylori with rosacea. However, this role is still being debated. Eradication of H. pylori can be achieved using a triple therapy regimen lasting 1 to 2 weeks [omeprazole and a combination of two antibacterials (a choice from clarithromycin, metronidazole or amoxicillin)]. Both the flashlamp-pumped long-pulse dye laser and the potassium-titanyl-phosphate laser may be used in the treatment of facial telangiectases.Both systemic and topical remedies may be used to treat the papulopustules of rosacea. Systemic treatment includes metronidazole, doxycycline, minocycline, clarithromycin and isotretinoin, while topical treatment is based on metronidazole cream and gel. The presence of Demodex folliculorum is important in the inflammatory reaction, whether it is pathogenetic or not. Crotamiton 10% cream or permethrin 5% cream may be useful medications for papulopustular rosacea, although they are rarely successful in eradicating D. folliculorum. Oral or topical ivermectin may also be useful in such cases.Ocular involvement is common in patients with cutaneous rosacea and can be treated with orally administered or topical antibacterials.Once rhinophyma starts to be evident, the only way to correct it is by aggressive dermatosurgical procedures. Decortication and various types of lasers can also be used.Associated conditions, such as seborrheic dermatitis and possible contact sensitizations, deserve attention.

The new cutaneous mucinoses: A review with an up-to-date classification of cutaneous mucinoses

In the past years seven new cutaneous mucinoses have been described. These are briefly reviewed and included in a revised classification of cutaneous mucinoses.

Pityriasis rosea: An update with a critical appraisal of its possible herpesviral etiology

Pityriasis rosea is an acute, self-healing exanthem characterized by oval erythematous-squamous lesions of the trunk and limbs, that usually spares face, scalp, palms, and soles. Constitutional symptoms, which have the character of true prodromes; clinical features, which resemble those of the known exanthems; and many epidemiologic data all suggest an infectious origin. A host of infectious agents have been incriminated, but, recently, human herpesvirus 6 and 7 have been extensively studied. The goal of this review is to outline the epidemiologic, clinical, histologic, and ultrastructural features of pityriasis rosea, but mainly to stress its possible human herpesvirus nature. In addition, clues have been added to help the reader to go through the complex subtleties of the virologic investigation.

Small Intestinal Bacterial Overgrowth in Rosacea: Clinical Effectiveness of Its Eradication

BACKGROUND & AIMS To better understand the role of small intestinal bacterial overgrowth (SIBO) in rosacea, we aimed to assess the presence of SIBO in patients with rosacea and the clinical effectiveness of its eradication. METHODS We enrolled 113 consecutive rosacea ambulatory patients (31 M/82 F; mean age, 52 +/- 15 years) and 60 healthy controls who were sex- and age-matched. Patients and controls underwent lactulose and glucose breath tests (BTs) to assess the presence of SIBO. Patients positive for SIBO were randomized to receive rifaximin therapy (1200 mg/day for 10 days) or placebo. A group of patients with negative BTs were also treated with rifaximin. Eradication was assessed 1 month after the end of therapy. Two dermatologists, unblinded on therapy, evaluated rosacea patients before and after treatment on the basis of an objective scale. RESULTS The prevalence of SIBO was higher in patients than controls (52/113 vs 3/60, P < .001). After eradication, cutaneous lesions cleared in 20 of 28 and greatly improved in 6 of 28 patients, whereas patients treated with placebo remained unchanged (18/20) or worsened (2/20) (P < .001). Placebo patients were subsequently switched to rifaximin therapy, and SIBO was eradicated in 17 of 20 cases. Fifteen had a complete resolution of rosacea. After antibiotic therapy, 13 of 16 patients with negative BTs for SIBO remained unchanged, and this result differed from SIBO-positive cases (P < .001). CONCLUSIONS This study demonstrated that rosacea patients have a significantly higher SIBO prevalence than controls. Moreover, eradication of SIBO induced an almost complete regression of their cutaneous lesions and maintained this excellent result for at least 9 months.

Cytomegalovirus infection in normal and immunocompromised humans. A review.

Although cytomegalovirus (CMV) disease is a severe complication among immunocompromised patients, its cutaneous features have not been reported frequently. CMV belongs to the Herpesviridae family sharing with the other members the ability to remain latent in their natural hosts after an initial infection and to produce overt disease in several settings. The natural history of human CMV infection is characterized by primary infection, latent infection and reinfection. This article reviews the extremely variable aspects of the clinical presentation of CMV infection in normal and immunocompromised humans, focusing on the dermatological manifestations, and indicates the laboratory tests for detecting CMV responsibility in skin disorders.

May Helicobacter pylori be important for dermatologists

Helicobacter pylori, a microaerophilic gram-negative bacterium, is the major cause of gastritis, plays a key role in the etiology of peptic ulcer and is a risk factor for gastric cancer. Although 50% of the population is affected, dermatologist seem to be unaware of the impact H. pylori may have on cutaneous pathology. Among skin diseases, H. pylori has been related so far only with chronic urticaria and rosacea. In rosacea, histology of the stomach mucosa revealed tht 84% of 31 patients were H. pylori positive. Twenty percent of them were serologically negative, but, overall, 100% of the 20 patients with both histology and serology were H. pylori positive with either test. The consistency between clinical success with metronidazole and abatement of H. pylori isolates and serology after treatment was an additional evidence suggesting an etiologic relationship between rosacea and H. pylori infection. Rosacea has often been linked with gastrointestinal disturbances. H. pylori, therefore, may link them to the well-known beneficial activity of metronidazole on rosacea lesions. The role of H. pylori is more probable in erythrotic rosacea than in its papulopustular and granulomatous stages. As in Bacillus subtilis intoxication, a flush-inducing toxin cannot be excluded. Despite the difficulty to find patients accepting bioptic gastroscopies, large case-control studies should be done before a causal relationship with urticaria and rosacea is firmly established.

THE SPECTRUM OF DOWLING‐DEGOS DISEASE

Dowling-Degos disease (DDD) has enjoyed a considerable resurgence of interest since Wilson-Jones and Grice drew attention to it in 1978. Eleven more cases have been described (Bardach, 1981; Grosshans et al., 1980; Brown, 1982; Ochiai & Yamaguchi, 1982; Crovato, Nazzari & Rebora, 1983) and its genetic transmission has been elucidated (Brown, 1982; Crovato et al., 1983). We have noticed an intriguing relationship between DDD and other rare genetic disorders, especially Habers syndrome (HS) (Crovato & Rebora, 1982; Kikuchi, 1982, 1983) and Kitamuras acropigmentatio reticularis (KAR) (Crovato, Desirello & Rebora, 1983). We believe that DDD is only one facet of a more extensive and complex genodermatosis, including some isolated cases that have previously been recorded under diflFerent titles. The aim of this paper is to propose a spectrum of diseases that present with different clinical features but with a unique histopathological picture of epidermal budding and extensive proliferation of the foUicular walls. We will therefore review the reported cases of DDD, HS and KAR, together with those showing similar features, gathering them into a coherent entity.

Clinical and laboratory presentation of lichen planus patients with chronic liver disease

A recent case-control study on 577 lichen planus (LP) patients and 1008 controls confirmed that LP patients may significantly associate with a chronic liver disease (CLD) which is independent from drug or alcohol intake and has some connection with hepatitis B virus (HBV) infection. The study, however, failed to define the nature of CLD. This has been investigated through the clinical and laboratory features of 50 patients with LP and impaired liver function tests. Overall, the laboratory signs of cell necrosis prevailed over those of cholestasis and a good relationship with the HBV and HCV infections was found. Ninety percent of patients with LP and CLD had antibodies to one or another of the major viruses involved in infectious hepatitis. No patient had anti-liver kidney microsomal antibodies type 1. Liver biopsies were done in 12 cases and mostly revealed a chronic active hepatitis evolving into cirrhosis. No evident cases of primary biliary cirrhosis were found. It appears that LP associated CLD is post-viral in nature.