CLINICAL REPORT
355 ActaDV ActaDV Advances in dermatology and venereology Acta Dermato-Venereologica
Granuloma Annulare and Morphea: Correlation with Borrelia burgdorferi Infections and Chlamydia-related Bacteria
Lauri TOLKKI 1 #, Kati HOKYNAR 2 #, Seppo MERI 3, Jaana PANELIUS 1, Mirja PUOLAKKAINEN 2 and Annamari RANKI 1
1
Department of Dermatology, Allergology and Venereal Diseases, University of Helsinki and Center of Inflammation, Helsinki University Central Hospital, 2 Department of Virology, and 3 Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland
#
These authors contributed equally to this paper.
A retrospective study of 109 skin biopsies with granuloma annulare( GA) or morphea histology from patients with suspected tick bite was performed. Biopsies were tested for cutaneous Borrelia burgdorferi DNA using PCR. The same biopsies were analysed for tick-borne novel agents, Chlamydia-related bacteria( members of the Chlamydiales order), using a PCRbased method. Borrelia DNA was detected in 7 / 73( 9.6 %) biopsies with GA and in 1 / 36( 2.8 %) biopsies with morphea, while Chlamydiales DNA was found in 53 / 73( 72.6 %) biopsies with GA and 25 / 34( 73.4 %) biopsies with morphea. All Borrelia DNA-positive GA samples were also positive for Chlamydiales DNA. The Chlamydiales sequences detected in GA were heterogeneous and contained Waddliaceae and Rhabdochlamydiaceae bacteria, which are also present in Ixodes ricinus ticks, while the Chlamydiales sequences detected in morphea closely resembled those found in healthy skin. In conclusion, tick-mediated infections can trigger GA in some cases, while correlation of either Borrelia or Chlamydiales with morphea is unlikely.
Key words: granuloma annulare; morphea; Borrelia burgdorferi; chlamydia-related bacteria.
Accepted Oct 31, 2017; Epub ahead of print Nov 7, 2017 Acta Derm Venereol 2018; 98: 355 – 360.
Corr: Lauri Tolkki, Center of Inflammation, Department of Dermatology, Allergology and Venereal Diseases, Helsinki University Central Hospital, PO Box 160, FIN-00029 Helsinki, Finland. E-mail: Lauri. Tolkki @ hus. fi
Granuloma annulare( GA) and morphea( localized scleroderma) are skin reactions with unknown aetiology( 1 – 5). One of the possible causative agents is Borrelia burgdorferi sensu lato, a spirochete transmitted to humans via tick bites. Although the causal connections between B. burgdorferi and GA and morphea have been explored in several studies using various methods, including indirect serological methods and direct detection by PCR, there is no firm evidence of a causative role( 6 – 11).
In addition to B. burgdorferi sensu lato, ticks are known to serve as vectors for a number of other animal and human pathogens, such as Babesia microti, which causes babesiosis, Anaplasma phagocytophilum, which causes human granulocytic anaplasmosis, species of the spotted fever group of Rickettsiae, and Flavivirus, which causes tick-borne encephalitis( TBE)( 12 – 15).
Recently, Ixodes ricinus ticks have also been shown to carry another group of potential human pathogens,
Chlamydia-related bacteria( 16 – 19). They share the characteristic features of the order Chlamydiales: strict intracellular lifestyle, biphasic developmental cycle and a large core-set of genes. The traditional members of the order are the established human pathogens Chlamydia trachomatis and Chlamydia pneumoniae( genus Chlamydia, family Chlamydiaceae). During the last 20 years, an increasing number of novel chlamydial species have been described and, currently, 8 additional families are recognized as belonging to the Chlamydiales order. These new families: Parachlamydiaceae, Waddliaceae, Simkaniaceae, Rhabdochlamydiaceae, Criblamydiaceae, Piscichlamydiaceae, Clavichlamydiaceae and Parilichlamydiaceae are collectively called Chlamydiarelated bacteria. They were originally detected in various types of environmental samples( e. g. soil and water from various sources), but subsequently also in animals, including arthropods, and humans. Many of them have pathogenic potential( 20, 21), and their reservoirs, vectors and transmission routes have been widely investigated, but have mainly remained obscure.
In this study, 109 patient skin biopsies with histologically confirmed GA and localized scleroderma( morphea) were analysed retrospectively. The samples had been studied for the presence of B. burgdorferi, either because of a clinical suspicion of borreliosis or because of abundant plasma cells in the biopsy. In order to determine whether certain types of Chlamydia-related bacteria could play a role in the pathogenesis of these conditions, the occurrence and type( s) of Chlamydiales in the biopsies was examined, and the results compared with our previously published data on healthy skin and ticks( 17). We recently reported the occurrence of Chlamydiales in up to 40 % of Finnish ticks and, furthermore, in human skin biopsies. Chlamydiales DNA was found in human skin samples, with a prevalence of 49 % in healthy skin( 19 / 39, 49 %) and 85 % in skin samples from subjects positive for B. burgdorferii PCR. This suggests that ticks could indeed serve as vectors for transmission of Chlamydia-related bacteria.
MATERIALS AND METHODS Patients
Data for all patients whose skin biopsies had a histology of GA or morphea and were submitted to B. burgdorferi DNA analysis
This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2018 Acta Dermato-Venereologica. doi: 10.2340 / 00015555-2831 Acta Derm Venereol 2018; 98: 355 – 360