Comparative analysis of immunohistochemistry, polymerase chain reaction and focus-floating microscopy for the detection of Treponema pallidum in mucocutaneous lesions of primary, secondary and tertiary syphilis

Müller, Hansgeorg; Eisendle, Klaus; Bräuninger, Wolfgang; Kutzner, Heinz; Cerroni, Lorenzo; Zelger, Bernhard

doi:10.1111/j.1365-2133.2011.10314.x

Cited by 50 publications

(44 citation statements)

References 36 publications

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“…Herein, we used IHC staining techniques to analyze four SS skin biopsies and corroborate that the cellular infiltrates were in agreement with previously published IHC analysis [32], [38], [56], [58] and to explore potential mechanisms for immune recognition of spirochetes within tissues. Substantial numbers of dermal mononuclear cells expressed the macrophage marker CD68 (Table S3 and Figure 7A and B ) [59].…”

Section: Resultssupporting

confidence: 80%

Immune Evasion and Recognition of the Syphilis Spirochete in Blood and Skin of Secondary Syphilis Patients: Two Immunologically Distinct Compartments

et al. 2012

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Background The clinical syndrome associated with secondary syphilis (SS) reflects the propensity of Treponema pallidum ( Tp ) to escape immune recognition while simultaneously inducing inflammation. Methods To better understand the duality of immune evasion and immune recognition in human syphilis, herein we used a combination of flow cytometry, immunohistochemistry (IHC), and transcriptional profiling to study the immune response in the blood and skin of 27 HIV(-) SS patients in relation to spirochetal burdens. Ex vivo opsonophagocytosis assays using human syphilitic sera (HSS) were performed to model spirochete-monocyte/macrophage interactions in vivo . Results Despite the presence of low-level spirochetemia, as well as immunophenotypic changes suggestive of monocyte activation, we did not detect systemic cytokine production. SS subjects had substantial decreases in circulating DCs and in IFNγ-producing and cytotoxic NK-cells, along with an emergent CD56−/CD16+ NK-cell subset in blood. Skin lesions, which had visible Tp by IHC and substantial amounts of Tp -DNA, had large numbers of macrophages (CD68+), a relative increase in CD8+ T-cells over CD4+ T-cells and were enriched for CD56+ NK-cells. Skin lesions contained transcripts for cytokines (IFN-γ, TNF-α), chemokines (CCL2, CXCL10), macrophage and DC activation markers (CD40, CD86), Fc-mediated phagocytosis receptors (FcγRI, FcγR3), IFN-β and effector molecules associated with CD8 and NK-cell cytotoxic responses. While HSS promoted uptake of Tp in conjunction with monocyte activation, most spirochetes were not internalized. Conclusions Our findings support the importance of macrophage driven opsonophagocytosis and cell mediated immunity in treponemal clearance, while suggesting that the balance between phagocytic uptake and evasion is influenced by the relative burdens of bacteria in blood and skin and the presence of Tp subpopulations with differential capacities for binding opsonic antibodies. They also bring to light the extent of the systemic innate and adaptive immunologic abnormalities that define the secondary stage of the disease, which in the skin of patients trends towards a T-cell cytolytic response.

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Section: Resultssupporting

confidence: 80%

Immune Evasion and Recognition of the Syphilis Spirochete in Blood and Skin of Secondary Syphilis Patients: Two Immunologically Distinct Compartments

et al. 2012

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“…Materiałem do badań mogą być tkanki, płyn mó-zgowordzeniowy (PMR), krew (metoda o niskiej czułości) itp. [14][15][16][17][18][19][20]. Nie istnieje na świecie jedna platforma PCR zaakceptowana do diagnostyki kiły, dlatego należy używać tylko metod poddanych dokładnej walidacji i z zastosowaniem odpowiedniej kontroli jakości.…”

Section: Diagnostyka Laboratoryjnaunclassified

“…• Metoda immunohistochemiczna z zastosowaniem poliklonalnych przeciwciał przeciwko T. pallidum może być skuteczna w identyfikacji krętków w zmianach skórnych, śluzówkowych lub w narządach wewnętrznych [19,20].…”

Section: Diagnostyka Laboratoryjnaunclassified

2014 European guideline on the management of syphilis

Janier¹,

Hegyi²,

Dupin³

et al. 2015

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“…Although the present case had an impressive persistent big crusted plaque for ten years which is much longer than the natural history of secondary syphilis, the histological feature was fully consistent with the change of secondary syphilis [9] and was lacking granulomatous inflammation with palisaded macrophages and fibroblasts which typically would be seen in tertiary syphilis [10]. Spirochetes were found by immunohistochemistry in our patient’s skin lesions whereas they are rarely visualized in patients with tertiary syphilis [11]. Thus, we consider that the diagnosis of secondary syphilis would be more reasonable than tertiary syphilis…”

Section: Discussionmentioning

confidence: 53%

Acute monoarthritis in a delayed diagnosis of syphilis patient with persistent rupioid psoriasis-like lesions

et al. 2012

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BackgroundThe incidence of syphilis is increasing in many parts of the world. Clinicians may have limited experience in the diagnosis when the clinical appearance is unusual. If early diagnosis is not made and prompt treatment not given, then the disease may remain quiescent until more serious symptoms or systemic involvement develops.Case presentationWe report the first case of a delayed diagnosis of syphilis with a ten-year history of persistent rupioid psoriasis-like lesions. Acute monoarthritis and high fever together with aggravation of skin lesions led to a careful clinical examination. Skin biopsies demonstrated syphilis spirochetes on immunohistochemical stain, and syphilis serological titers were positive. Standard treatment with benzathine penicillin brought a partial and transient improvement. A complete clinical and serological resolution of the disease was achieved by a prolonged and repeated penicillin treatment combined with methylprednisolone. A 7-year follow-up of the patient proved a full recovery.ConclusionOur case highlights the fact that clinical signs of syphilis can be diverse and complicated. Unusual clinical manifestations can happen in an immunocompetent individual. Treatment strategy may need to be adjusted in a difficult case.

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Comparative analysis of immunohistochemistry, polymerase chain reaction and focus-floating microscopy for the detection of Treponema pallidum in mucocutaneous lesions of primary, secondary and tertiary syphilis

Cited by 50 publications

References 36 publications

Immune Evasion and Recognition of the Syphilis Spirochete in Blood and Skin of Secondary Syphilis Patients: Two Immunologically Distinct Compartments

Immune Evasion and Recognition of the Syphilis Spirochete in Blood and Skin of Secondary Syphilis Patients: Two Immunologically Distinct Compartments

2014 European guideline on the management of syphilis

Acute monoarthritis in a delayed diagnosis of syphilis patient with persistent rupioid psoriasis-like lesions

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