[Cutaneous manifestations of Lyme disease : Pitfalls in the serological diagnostic workup]. / Kutane Lyme-Borreliose : Fallstricke der serologischen Diagnostik.

Serology, the detection of B. burgdorferi-specific IgM and IgG serum antibodies, is the most common laboratory test to diagnose cutaneous manifestations of Lyme disease. In a two-tiered approach, an ELISA is used as a screening test. A positive or equivocal ELISA result needs confirmation by a specific immunoblot. The sensitivity of this approach reaches 80-95%. The diagnosis of erythema migrans is based on its typical clinical appearance. Serology is only indicated in atypical cases. In contrast, serology is mandatory in the diagnostic workup of borrelial lymphocytoma and acrodermatitis chronica atrophicans. A positive serology can persist for many years, even after adequate antibiotic treatment. A positive serology is no indication for antibiotic treatment if typical symptoms of Lyme disease are absent.

[Skin infections in pregnancy]. / Hautinfektionen in der Schwangerschaft.

The article outlines examples of a viral (varicella-zoster virus, VZV), a bacterial (Lyme borreliosis) and a parasitic (scabies) infection in pregnancy with their risk for the mother and/or child as well as their management. VZV infections cause various clinical scenarios depending on the maternal immune status and the time of infection. Herpes zoster usually poses no risk to the pregnant woman and there is no need for antiviral therapy. VZV infection of a seronegative mother, however, may lead to severe varicella in the pregnant woman and to congenital malformations (congenital varicella syndrome) in case of early infection or neonatal varicella in case of perinatal infection. Prompt therapy with acyclovir or administration of VZV immunoglobulin for prophylaxis is mandatory in those patients. In case of Lyme borreliosis of the mother, adequate antibiotic therapy with amoxicillin prevents harm to the fetus. Doxycycline is contraindicated during pregnancy. Scabies represents an important differential diagnosis of pruritic dermatoses in pregnancy and should be treated with permethrin 5% cream.

Is serological follow-up useful for patients with cutaneous Lyme borreliosis?

Serologic follow-up examinations are frequently performed in patients with erythema migrans, borrelial lymphocytoma, and acrodermatitis chronica atrophicans (the 3 dermatoborrelioses) to evaluate treatment efficacy. There is, however, substantial proof in the literature that antibody titer development after therapy is unpredictable and variable, and moreover it is largely uncorrelated with the clinical course and mode of antibiotic treatment. For example, persistent positive IgG and/ or IgM antibody titers do not indicate treatment failure. Thus, repeated serologic testing is of very limited value for assessing therapy efficacy, and therefore not recommended in the follow-up of dermatoborrelioses patients. Since cultivation of the etiologic agent, Borrelia burgdorferi sensu lato, and polymerase chain reaction are also inadequate for this purpose, the assessment of patients with cutaneous manifestations of Lyme borreliosis in the follow-up rests primarily on the clinical picture.

The impact of immunosuppression on erythema migrans. A retrospective study of clinical presentation, response to treatment and production of Borrelia antibodies in 33 patients.

BACKGROUND: Little is known about the potential influence of immunosuppression on erythema migrans, the hallmark of early Lyme borreliosis. METHODS: We performed a retrospective study to assess the impact of immunosuppression on erythema migrans in 33 patients with a malignant or autoimmune disease, chronic infection, or immunosuppressive therapy for organ transplantation. Only patients with active disease status and/or current immunosuppressive therapy were included. Pre-treatment clinical parameters, such as presentation of the skin lesion and presence of extracutaneous signs and symptoms, the disease course during a median follow-up of 9 months after therapy and serum anti-Borrelia burgdorferi antibodies before therapy and by the end of follow-up in the 33 immunosuppressed patients were statistically compared with 75 otherwise healthy patients with erythema migrans. The 75 control patients were matched for sex, age and antibiotic therapy. RESULTS: With the exception of the site of erythema migrans lesions, which were found more often on the trunk than on the legs in the immunosuppressed patients (vice versa in immunocompetent patients), we found no significant differences for all investigated parameters between the two groups. CONCLUSIONS: It appears that immunosuppression does not influence clinical presentation, response to therapy, or production of anti-B. burgdorferi antibodies of patients with erythema migrans. It is thus not necessary to treat immunosuppressed patients with erythema migrans differently from immunocompetent patients.

Polymorphic eruption of pregnancy: clinicopathology and potential trigger factors in 181 patients.

BACKGROUND: Polymorphic eruption of pregnancy (PEP; synonym: pruritic urticarial papules and plaques of pregnancy) is the most common specific dermatosis of pregnancy. However, its clinical characterization is controversial and its pathogenesis uncertain. OBJECTIVES: To evaluate clinical characteristics of and potential trigger factors for PEP in a large mixed ethnic population. METHODS: A retrospective analysis of epidemiological, clinical, immunopathological and obstetric findings in 181 patients with PEP seen at two university-based dermatological hospitals in Graz, Austria, and London, U.K. RESULTS: PEP mainly affected white (88%) primigravidae (70%) in late pregnancy (83%; mean +/- SD onset 34 +/- 5 weeks) or the immediate postpartum period (15%). The most commonly involved sites were the abdomen and proximal thighs (97%). Involvement of the whole skin, including the face, palms and soles, was only rarely observed. While pruritic urticarial papules and plaques were the main morphological features at disease onset (98%), more than one-half of the patients (51%) later developed polymorphous features including erythema, vesicles, and targetoid and eczematous lesions. Topical treatment with corticosteroids and emollients was sufficient to control symptoms in the majority of patients, and skin lesions resolved after a mean +/- SD of 4 +/- 3 weeks. Multiple gestation pregnancies were observed in 13% of cases, excessive maternal weight gain in 78%. CONCLUSIONS: Our data confirm the benign, self-limiting nature of PEP and its favourable outcome for both the mother and the fetus. For the first time, we have documented a characteristic change in morphology with disease progression. The evidence of polymorphous clinical features in more than one-half of the patients favours the use of the term PEP. Multiple gestation pregnancies and excessive maternal weight gain, but not fetal weight and sex, were found to be significantly associated with PEP.

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.

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.

Differential expression of cytokine mRNA in skin specimens from patients with erythema migrans or acrodermatitis chronica atrophicans.

Erythema migrans, the characteristic skin manifestation of acute Lyme borreliosis, is a self-limited lesion. In contrast, acrodermatitis chronica atrophicans, the typical cutaneous manifestation of late Lyme borreliosis, is a chronic skin condition. In an effort to understand pathogenic factors that lead to different outcomes in dermatoborrelioses, skin biopsy samples from 42 patients with erythema migrans and 27 patients with acrodermatitis chronica atrophicans were analyzed for mRNA expression of five pro-inflammatory cytokines (tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, interferon-gamma, and interleukin-2) and two anti-inflammatory cytokines (interleukin-4 and interleukin-10) by in situ hybridization with cytokine-specific riboprobes. Among the 27 patients who had erythema migrans alone with no associated signs or symptoms, the major cytokines expressed in perivascular infiltrates of T cells and macrophages were the pro-inflammatory cytokine interferon-gamma and the anti-inflammatory cytokine interleukin-10. In the 15 erythema migrans patients who had associated signs and symptoms, including headache, elevated temperature, arthralgias, myalgias, or fatigue, a larger number of macrophages and greater expression of macrophage-derived pro-inflammatory cytokines, tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6, were also found. In comparison, infiltrates of T cells and macrophages in the skin lesions of acrodermatitis chronica atrophicans patients had very little or no interferon-gamma expression. Instead, they usually expressed only the pro-inflammatory cytokine tumor necrosis factor alpha and the anti-inflammatory cytokine interleukin-4. Thus, the activation of pro-inflammatory cytokines in erythema migrans lesions, particularly interferon-gamma, seems to be important in the control of the spirochetal infection. In contrast, the restricted pattern of cytokine expression in acrodermatitis chronica atrophicans, including the lack of interferon-gamma, may be less effective in spirochetal killing, resulting in the chronicity of this skin lesion. J Invest Dermatol 115:1115-1123 2000

Topical treatment with liposomes containing T4 endonuclease V protects human skin in vivo from ultraviolet-induced upregulation of interleukin-10 and tumor necrosis factor-alpha.

Exposing human skin to ultraviolet radiation causes DNA damage, sunburn, immune alterations, and eventually, skin cancer. We wished to determine whether liposomes containing a DNA repair enzyme could prevent any of the acute effects of irradiation when applied after ultraviolet exposure. Fifteen human patients with a prior history of skin cancer were exposed to two minimal erythema doses of ultraviolet radiation on their buttock skin. Liposomes containing T4 endonuclease V or heat-inactivated enzyme were applied immediately and at 2, 4, and 5 h after ultraviolet irradiation. Transmission electron microscopy after anti-T4 endonuclease V-staining and immunogold labeling on biopsies taken at 6 h after ultraviolet exposure revealed that the enzyme was present within cells in the skin. Immunohistochemical DNA damage studies suggested a trend toward improved DNA repair at the active T4 endonuclease V liposome-treated test sites. Although the active T4 endonuclease V liposomes did not significantly affect the ultraviolet-induced erythema response and microscopic sunburn cell formation, they nearly completely prevented ultraviolet-induced upregulation of interleukin-10 and tumor necrosis factor-alpha RNA message and of interleukin-10 protein. These studies demonstrate that liposomes can be used for topical intracellular delivery of small proteins to human skin and suggest that liposomes containing DNA repair enzymes may provide a new avenue for photoprotection against some forms of ultraviolet-induced skin damage.

Lyme borreliosis of central nervous system (CNS) in children: a diagnostic challenge.

Within 24 months in a consecutive series of 84 children with neurological symptoms indicative of Lyme borreliosis of the central nervous system (CNS) 45 seronegative children (group III), 17 seropositive (group II), and 22 children with specific Borrelia burgdorferi results in cerebrospinal fluid (CSF)-i.e. B. burgdorferi antibodies and/or intrathecally produced B. burgdorferi antibodies and/or positive B. burgdorferi culture in CSF were observed. The results show that intrathecally produced B. burgdorferi antibodies are the most important marker for the diagnosis of neuroborreliosis (with 71.4% positives) and B. burgdorferi cultivation directly from CSF may be successful in the earliest phase of the disease. Since each of the specific CSF parameters may be false negative in some cases, a careful synopsis of laboratory parameters was done. It shows that CSF protein and CSF cell values are higher in group I than in II or III. Neither can seronegativity exclude nor can seropositivity confirm the diagnosis of neuroborreliosis as in only 71% of group I serum B. burgdorferi antibodies were detected. In view of these aspects clinical and laboratory results are discussed.

Penicillin G sodium and ceftriaxone in the treatment of neuroborreliosis in children--a prospective study.

A controlled clinical study was set up to examine whether penicillin G sodium (PG) or ceftriaxone (C) is superior in the treatment of acute neuroborreliosis in childhood. Within a time period of 18 months 77 children with symptoms indicative of Lyme borreliosis of the central nervous system (CNS) were seen. In 23 of these children Borrelia burgdorferi specific cerebrospinal fluid (CSF) parameters confirmed the diagnosis of a neuroborreliosis. These children were treated at random with intravenous (i.v.) PG 400,000-500,000 I.U./kg/day for 14 days (group I) or with i.v. ceftriaxone 75-93 mg/kg/day for 14 days (group II), respectively. Clinical examination and a set of diagnostic laboratory parameters were done at admission, right after therapy, three, six and partly 12 months after therapy. The general condition of all children in both groups improved dramatically during antibiotic therapy, and no relapse occurred within the observation period. Considering the clear and comparable decrease of B. burgdorferi serum titres and the clinical outcome (duration of disease and follow-up for at least six months) in children of both groups no difference between both antibiotic drugs can be demonstrated.

Preliminary characterization of Borrelia burgdorferi CSF isolates.

Borrelia burgdorferi was cultivated from three cerebrospinal fluid (CSF) samples of children (aged three and a half, four and a half and eight years) who were admitted to the hospital because of acute facial palsy, aseptic meningitis, and aseptic meningitis plus facial palsy. CSF was taken on day one in two cases and on day two in the remaining case after onset of symptoms. All three strains showed a very similar SDS-PAGE pattern, without an OspB and 20kD band. However, of nine monoclonal antibodies (Moab) raised against B. burgdorferi B31, the Moab H5332 recognized two strains, one of them very weakly, and the flagella specific Moabs H9724, H605, and H6TS (less intensively) recognized all strains. This preliminary characterization reveals heterogeneity among CSF Borrelia isolates of cases from a very close geographic area.