Klaus Eisendle

Focus Floating Microscopy“Gold Standard” for Cutaneous Borreliosis?

Borrelia burgdorferi is difficult to detect in routine biopsy material from patients with skin lesions of borreliosis. In this study, a new immunohistochemical method, focus floating microscopy (FFM), was developed to detect B burgdorferi in tissue sections and was compared with polymerase chain reaction (PCR). By using standard histologic equipment, tissue sections stained with a polyclonal B burgdorferi antibody were simultaneously scanned through 2 planes: horizontally in serpentines and vertically by focusing through the thickness of the section. Borrelia were detected in 47 of 71 ticks, 34 of 66 tick bites, 30 of 32 erythema chronicum migrans cases, 41 of 43 borrelial lymphocytomas, and 50 of 51 acrodermatitis chronica atrophicans cases. FFM proved to be more sensitive than PCR (96.0% vs 45.2%) and nearly equally specific (99.4% vs 100%). All 169 control cases, except 1 false-positive case of secondary syphilis, were negative with FFM. FFM is an easy, quick, and inexpensive method to reliably detect Borrelia in cutaneous tissue sections.

Morphoea: a manifestation of infection with Borrelia species?

Background  Morphoea or localized scleroderma is a cutaneous inflammatory disease with still unknown aetiology. Borrelia burgdorferi as causative agent has been discussed controversially.

Effect of the dual endothelin receptor antagonist bosentan on Raynaud’s phenomenon secondary to systemic sclerosis: a double-blind prospective, randomized, placebo-controlled pilot study

OBJECTIVE To investigate the efficacy of the endothelin receptor antagonist, bosentan, in patients with RP secondary to SSc without pre-existing digital ulcers. METHODS Single-centre, randomized, prospective, double-blinded comparison of bosentan and placebo. Patients received either 62.5 mg bosentan twice daily for 4 weeks, followed by 125 mg twice daily for 12 weeks or matching doses of placebo. RESULTS Of the 17 patients enrolled, 16 completed the study and 1 withdrew from the study due to the reversible development of peripheral oedema. Compared with placebo, bosentan did not improve the frequency, duration, pain or severity of RP attacks. However, in contrast to placebo, bosentan significantly improved the functional scores. With respect to baseline, the scleroderma HAQ disability index changes were in favour of bosentan at Weeks 12 (P = 0.03) and 20 (P = 0.01), and the United Kingdom functional score changes at Weeks 8 (P = 0.038) and 16 (P = 0.039). CONCLUSIONS Bosentan is not effective in SSc-related RP without pre-existing digital ulcers, but it might benefit functional impairment in those patients. TRIAL REGISTRATION European Union Drug Regulating Authorities Clinical Trials, https://eudract.emea.europa.eu, EudraCT-Nr 2004-002686-21.

New concepts on erythema annulare centrifugum: a clinical reaction pattern that does not represent a specific clinicopathological entity.

Background  Erythema annulare centrifugum (EAC) is considered an inflammatory skin disease with unknown aetiology. In most textbooks it is assigned to the incoherent conglomeration of figurate or gyrate erythemas.

Possible Role of Borrelia burgdorferi Sensu Lato Infection in Lichen Sclerosus

OBJECTIVE To assess the evidence for Borrelia burgdorferi sensu lato infection in patients with lichen sclerosus by focus-floating microscopy. SETTING Dermatology department of a university hospital. DESIGN Tissue sections were stained with a polyclonal B burgdorferi antibody using standard histological equipment and then scanned simultaneously in 2 planes: horizontally in a serpentine-like pattern and vertically by focusing through the thickness of the section, ie, focus-floating microscopy. Part of the material was also investigated by Borrelia-specific polymerase chain reaction. PATIENTS The study population comprised 61 cases of lichen sclerosus and 118 controls (60 negative controls and 68 positive controls). MAIN OUTCOME MEASURE The presence of B burgdorferi sensu lato within tissue specimens. RESULTS Using focus-floating microscopy, we detected Borrelia species in 38 of 60 cases (63%) of lichen sclerosus and in 61 of 68 (90%) of positive controls of classic borreliosis, but Borrelia species were absent in all negative controls. Borrelia species were detected significantly more often in early inflammatory-rich (31 of 39 [80%]) than in late inflammatory-poor (7 of 21 [33.3%]) cases (P = .001). Polymerase chain reaction findings were positive in 25 of 68 positive controls (37%) and negative in all 11 cases of lichen sclerosus and all 15 negative controls. CONCLUSIONS Focus-floating microscopy is a reliable method to detect Borrelia species in tissue sections. The frequent detection of this microorganism, especially in early lichen sclerosus, points to a specific involvement of B burgdorferi or other similar strains in the development or as a trigger of this disease.

Infliximab monotherapy as first-line treatment for adult-onset pityriasis rubra pilaris: Case report and review of the literature on biologic therapy

Pityriasis rubra pilaris (PRP) is a rare, chronic papulosquamous disorder of unknown etiology that often progresses to disabling palmoplantar keratoderma and erythroderma. There is currently no universally effective treatment for PRP, and some cases are resistant to multiple topical and systemic therapies. Systemic retinoids, methotrexate, several immunosuppressive agents, fumaric acid esters, stanozolol, and phototherapy have all been used with varying degrees of success. Recently, a few reports have appeared in the literature concerning the use of biologics in combination therapies and/or in refractory PRP cases. We report a case of type I adult-onset PRP successfully treated with infliximab monotherapy as initial systemic therapy, and provide a comprehensive literature review on biologic therapy for PRP. The complete and persistent response to infliximab in our patient and in the previously reported cases confirms a role for anti-tumor necrosis factor-alfa therapy as an effective option in the treatment of PRP. Further studies are warranted to evaluate possible differences in efficacy among the different biologics.

Phenotypic and functional deficiencies of leukaemic dendritic cells from patients with chronic myeloid leukaemia.

Summary. Chronic myeloid leukaemia (CML) dendritic cells (DC) are possible candidates for inducing antileukaemic immunity. This study aimed to investigate the frequency, phenotype and function of blood‐derived leukaemic DC in comparison with DC from healthy donors using flow cytometric assays and mixed leucocyte reaction (MLR). Immature leukaemic DC displayed a reduced endocytotic capacity as compared with healthy controls. Moreover, in vitro maturation of leukaemic DC was found to be deficient. Expression of CD80, CD83, CD86, and major histocompatibility complex class I and class II antigens were reduced on lipopolysaccharide (LPS)‐matured leukaemic DC but were enhanced by a mixture of interleukin 1β (IL‐1β), IL‐6, tumour necrosis factor‐α (TNF‐α) and prostaglandin E2 (PGE2). Upon stimulation with bacterial LPS, intracellular TNF‐α and IL‐8 production was diminished in maturing DC from CML patients. This distinct cytokine deficiency was overcome when leukaemic DC were stimulated with cytokines/PGE2. MLR showed fully functional leukaemic DC after TNF‐α‐induced maturation, but a reduced proliferative alloresponse of leukaemic peripheral blood mononuclear cells. Further, intracellular production of cytokines in CML‐derived T cells was markedly reduced. These data indicated that, in CML, the maturation response of leukaemic monocyte‐derived DC to a natural stimulus like LPS is abnormal and may be caused by an aberrant TNF‐α response in these cells. Thus, TNF‐α alone or in combination with pro‐inflammatory and T‐cell stimulatory cytokines should be considered as an adjuvant for DC‐based immunotherapy in CML.

Granuloma annulare--a manifestation of infection with Borrelia?

Background:  Among the theories of origin of granuloma annulare (GA) are those of infection. Reports gave raise to the assumption that there is evidence for Borrelia as the causing agent.

Lymphocytic infiltration of the skin (Jessner-Kanof) but not reticular erythematous mucinosis occasionally represents clinical manifestations of Borrelia-associated pseudolymphoma.

Background  Lymphocytic infiltration of the skin (LIS) and reticular erythematous mucinosis (REM) are characterized histologically by an inflammatory cutaneous lymphocytic infiltrate similar to the histological appearance of pseudolymphoma.

Comparison of metallothionein-overexpression with sentinel lymph node biopsy as prognostic factors in melanoma

Background  Metallothioneins (MT) are ubiquitous, intracellular small proteins with high affinity for heavy metal ions. Immunohistochemical MT overexpression in paraffin‐embedded tissues of patients with primary melanoma is associated with poor prognosis. While sentinel lymph node (SLN) biopsy is an established surgical technique for high‐risk melanoma patients with predictive value for progression, the benefit of this procedure for the individual patients overall survival remains unclear.