Robert R. Müllegger

Borrelia burgdorferi‐associated lymphocytoma cutis: clinicopathologic, immunophenotypic, and molecular study of 106 cases

Lymphocytoma cutis (LC) is considered as the stereotypical example of the cutaneous B‐cell pseudolymphomas. It can be induced by various antigenic stimuli including arthropod bites, vaccination, and drugs among others. In endemic regions, Borrelia burgdorferi is the principal causative agent for LC. We studied retrospectively 108 biopsies from 106 patients (male : female, 48 : 58; mean age, 44.6; median, 51.5; range, 3–81) with B. burgdorferi‐associated LC retrieved from the files of the Department of Dermatology of the University of Graz (Austria). Only cases with a B. burgdorferi etiology (typical locations, positivity of serologic and/or polymerase chain reaction (PCR) tests, clinical history) were included in the study. Lesions were located on the nipple (63 cases), earlobe (18 cases), genital region (9 cases), and trunk or extremities (16 cases). PCR analysis of B. burgdorferi DNA was positive in 54 of 80 cases tested (67.5%). In 47 cases, we could retrieve data on serologic examination for B. burgdorferi antibodies performed at the time of diagnosis of LC. Positivity was found in 45 patients (IgG+/IgM+, 5 cases; IgG+/IgM–, 37 cases; IgG–/IgM+, 3 cases; IgG–/IgM–, 2 cases). Histology revealed dense lymphoid infiltrates with prominent germinal centers (GCs) in all cases. Atypical morphologic and/or immunophenotypic features of the GCs were commonly observed. In 5 cases, due to confluence of large follicles, the histopathologic pattern simulated that of a large B‐cell lymphoma. PCR analysis of the IgH gene rearrangement performed in 33 cases showed a polyclonal pattern in 31 cases and a monoclonal band in 2. In summary, B. burgdorferi‐associated LC can present with misleading histopathologic, immunophenotypic, and molecular features, and integration of all data is necessary for a correct diagnosis.

Skin Manifestations of Lyme Borreliosis : Diagnosis and Management

Lyme borreliosis is a multisystem infectious disease caused by tick-transmitted spirochetes of the Borrelia burgdorferi sensu lato complex. The three characteristic cutaneous manifestations are erythema migrans, borrelial lymphocytoma, and acrodermatitis chronica atrophicans. Erythema migrans occurs in acute Lyme borreliosis, lymphocytoma is a subacute lesion, and acrodermatitis is the typical manifestation of late Lyme borreliosis. Clinical appearances of erythema migrans and lymphocytoma (when located on the ear or breast) are characteristic, whereas acrodermatitis is often confused with vascular conditions. The diagnosis of erythema migrans is made clinically. Serologic analyses often yield false-negative results and are not required for the diagnosis. However, serologic proof of the diagnosis in lymphocytoma (approximately 90% positive) and acrodermatitis (100% positive) is mandatory. Histopathologic examination often adds substantial information in patients with skin manifestations of Lyme borreliosis and is recommended in clinically (and serologically) undecided cases of erythema migrans or lymphocytoma and is obligatory in acrodermatitis. Polymerase chain reaction for Borrelia-specific DNA (rather than culture of the spirochete) and immunohistochemical investigations (lymphocytoma) are sometimes necessary adjuncts for the diagnosis. Antibacterial treatment is necessary in all patients to eliminate the spirochete, cure current disease, and prevent late sequelae. Oral doxycycline, also effective against coinfection with Anaplasma phagocytophilum, is the mainstay of therapy of cutaneous manifestations of Lyme borreliosis. Other first-line antibacterials are amoxicillin and cefuroxime axetil. Erythema migrans is treated for 2 weeks, lymphocytoma for 3–4 weeks, and acrodermatitis for at least 4 weeks.

Indolent CD8+ lymphoid proliferation of the ear: A phenotypic variant of the small-medium pleomorphic cutaneous T-cell lymphoma?

Background: Recently, Petrella et al. described four patients with an unusual CD8+ lymphoid proliferation arising on the ear. These cases do not correspond clearly to any recognized category of cutaneous T‐cell lymphoma (CTCL) described in the World Health Organization (WHO)/European Organization for Research and Treatment of Cancer (EORTC) 2005 classification.

Resolution of granulomatous rosacea after eradication of Helicobacter pylori with clarithromycin, metronidazole and pantoprazole.

The aetiopathogenetic role of Helicobacter pylori in rosacea remains controversial. We report a 27-year-old man with a 4-year history of intractable rosacea. Histopathology showed epithelioid granulomas. H. pylori infection was proven directly on gastroscopy and by serological testing. Treatment with clarithromycin, metronidazole and pantoprazole eradicated H. pylori. Skin changes were markedly improved by the end of this therapy and had resolved completely 2 months later. The patient has been followed up, and has remained free of symptoms for 3 years. We suggest that H. pylori may be involved in the aetiopathogenesis of granulomatous rosacea.

Human cowpox in a veterinary student

A 19-year-old previously well female veterinary student with regular contact with diverse species of animals presented with an initially small red plaque on her left cheek. During the next 3 weeks the lesion developed into an ulcerated nodule 4 cm in size with a brownish eschar on top, a satellite papule, and marked infl ammation of the surrounding skin (fi gure). The patient had malaise and a painful pronounced cervical lymphadenopathy. Laboratory investigations were unremarkable except for a transient elevation of C-reactive protein (820 mg/L), neutropenia (38%), and eosinophilia (11%). During 2 weeks of intravenous treatment with piperacillin and tazobactam combined fi rst with clindamycin then doxycycline, the nodule demarcated but persisted, and a complete necrectomy was done. The resulting large tissue defect was reconstructed in a separate operation. Serology for Francisella tularensis, Bartonella henselae, Yersinia enterocolitica O3 and O9 antigens, Leishmania spp, Rickettsia conorii, and R mooseri were all negative. Bacterial cultures were negative, including Bacillus anthracis and Mycobacterium tuberculosis. Histopathology showed full-thickness necrosis of the skin. Brick-shaped orthopoxvirus particles were evident on electron microscopy (fi gure) and quantitative real-time PCR of the haemagglutinin gene of the cowpox virus was positive, leading to the diagnosis of human cowpox. Sequence analysis by direct DNA sequencing identifi ed the isolate AT_Styria/84/09 (Genbank accession number FJ7692784) that is closely related to a cowpox virus isolated from domestic cats in Austria. Cowpox virus infections represent a very rare zoonosis in human beings. However, increasing numbers of cases in young people have been documented recently, presumably because of a lack of cross-reactive immunity after the end of routine smallpox vaccination in the late 1970s. The disease remains localised and is self-limiting in patients that are immunocompetent, although dissemination and fatal courses have been reported. After an incubation period of 7–12 days after direct skin contact with cats, which are the main source of infections in people, patients develop a necrotising nodule with consecutive scar formation, accompanied by malaise, raised temperature, and long-lasting, pronounced, and painful regional lymphadenopathy. Diagnosis is made on the basis of electron microscopy and PCR of the lesion. Although no approved specifi c antiviral treatment exists against infections with the cowpox virus, cidofovir can be given in complicated cases. Plastic surgery might be necessary to avoid substantial aesthetic consequences.

Successful outcome of haemodialysis-induced pseudoporphyria after short-term oral N-acetylcysteine and switch to high-flux technique dialysis.

Pseudoporphyria is a blistering disease with skin fragility and shallow scarring that clinically and histopathologically closely resembles porphyria cutanea tarda. The two conditions can be distinguished by porphyrin levels that typically are elevated in porphyria cutanea tarda, but not or only slightly in pseudoporphyria. Pseudoporphyria can be induced by various medications (e.g. non-steroidal anti-inflammatory drugs, antibiotics, diuretics, retinoids), intense UV(A) exposure, or haemodialysis. Treatment of haemodialysis-associated pseudoporphyria is not yet standardized. We report here a 65-year-old male patient with chronic renal failure due to Waldenströms macroglobulinaemia who was treated with conventional 3 times/week haemodialysis. He developed blistering skin changes on both hands, which were diagnosed as pseudoporphyria based on clinical, histopathological, and laboratory findings, and could be successfully managed with initial oral N-acetylcysteine and a switch from low-flux to high-flux membrane haemodialysis. The beneficial effect of the high-flux membrane technique in haemodialysis-associated pseudoporphyria has not been previously reported.

Grover's disease associated with Sarcoptes scabiei.

An 83-year-old man presented with a 4-month history of discrete, itchy papules mainly distributed on the trunk and upper extremities. Histopathologic examination of two biopsies from lesions on the trunk revealed mainly focal suprabasal acantholysis and an inflammatory infiltrate composed mainly of lymphocytes with a few eosinophils. The overall clinical and histopathologic features were consistent with Grover’s disease. However, scrapings taken from the skin lesions showed numerous mites of Sarcoptes scabiei. Subsequent treatment with an antiscabies cream led to a rapid complete cure, and no skin lesions have been observed during a 6-month follow-up. A review of the literature revealed 2 other cases of cutaneous lesions fulfilling the clinical and histopathologic features of Grover’s disease in which mites of S. scabiei were demonstrated. Our observation further highlights the unusual association of Grover’s disease with S. scabiei mites and emphasises the importance of excluding this easily treatable skin infestation in all patients with Grover’s disease.

Photoaccentuated erythroderma associated with CD4+ T lymphocytopenia: Successful treatment with 5-methoxypsoralen and UVA, interferon alfa-2b, and extracorporeal photopheresis

We describe a 53-year-old HIV-negative white man who had chronic CD4+ T lymphocytopenia and photoaccentuated erythroderma with lymphoma-like histologic changes. The erythroderma completely responded to 5-methoxypsoralen and UVA (PUVA), interferon alfa-2b, and extracorporeal photopheresis. During therapy opportunistic skin infections, including tinea corporis, warts, and disseminated molluscum contagiosum, developed. Although the patient met the current definition of idiopathic CD4+ T lymphocytopenia (ICTL), we cannot rule out the possibility that this peripheral CD4+ T lymphocytopenia resulted from sequestration of CD4+ T lymphocytes in erythrodermic skin.

Clinical spectrum of skin manifestations of Lyme borreliosis in 204 children in Austria.

The spectrum of skin manifestations of Lyme borreliosis in children is not well characterized. We conducted a retrospective study to analyze the clinical characteristics, seroreactivity to Borrelia burgdorferi sensu lato, and outcome after treatment in 204 children with skin manifestations of Lyme borreliosis seen in 1996-2011. Solitary erythema migrans was the most common manifestation (44.6%), followed by erythema migrans with multiple lesions (27%), borrelial lymphocytoma (21.6%), and acrodermatitis chronica atrophicans (0.9%). A collision lesion of a primary borrelial lymphocytoma and a surrounding secondary erythema migrans was diagnosed in 5.9% of children. Rate of seroreactivity to B. burgdorferi s.l. was lower in solitary erythema migrans compared to other diagnosis groups. Amoxicillin or phenoxymethylpenicillin led to complete resolution of erythema migrans within a median of 6 (solitary) and 14 days (multiple lesions), respectively, and of borrelia lymphocytoma within a median of 56 days. In conclusion, erythema migrans with multiple lesions and borrelial lymphocytoma appear to be more frequent in children than in adults, whereas acrodermatitis chronica atrophicans is a rarity in childhood. The outcome after antibiotic therapy was excellent in children, and appears to be better than in adults.

Skin infections in pregnancy

A wide array of infectious diseases can occur in pregnancy. Their acquisition, clinical presentation, and course during gestation may be altered due to an impairment of the maternal cellular immunity. Some infectious diseases can lead to serious consequences for the mother or the offspring, including congenital malformations. This review describes in detail the clinical presentation, course, management, and associated maternal and fetal risks of selected viral (varicella-zoster virus infections, condylomata acuminata), fungal (candida vulvovaginitis), bacterial (Lyme borreliosis), and parasitic (scabies) infections. The treatment options are critically reviewed. First-line therapies include acyclovir and varicella-zoster virus immunoglobulin for varicella-zoster virus infections, surgical modalities for genital warts, topical clotrimazole and oral fluconazole for Candida vulvovaginitis, amoxicillin and cefuroxime for Lyme borreliosis, and permethrin for scabies. A synopsis of maternal and fetal risks of other important infections is also included.