Division of Dermatology Dr A Motau
CASE 1
Histopathology H&E
H&E
H&E
Wartin Starry
Immunohistochemical stain for T. pallidum
Investigations FBC, U&E, LFT Normal T. pallidum Abs Reactive RPR screen Reactive RPR titre 32 Fungal Culture Negative
Case 2
Investigations Histopathology: - Irregular acanthosis, elongated rete ridges - Heavy infiltrate of plasma cells, granulomas - Wartin Starry: Negative - Immunohistochemical stain: Positive for T. pallidum Serology: - HIV Reactive CD4 count - 165 - T. pallidum Abs - Reactive - RPR screen Reactive - RPR titre - 1064
The Great Imitator
Introduction Diverse clinical manifestations Appropriately named the great imitator Atypical presentations common esp. HIV association Diagnostic + treatment delays may often lead to devastating complications
Epidemiology Major health problem, esp. in low income countries and is leading cause GUD Re-emerged in several high-income countries WHO estimates 11 million new cases reported globally, per annum In USA >75% cases were diagnosed in homosexual males
Aetiopathogenesis Causative organism T. pallidum Chronic systemic sexually transmitted disease Inoculation and penetration occur via mucosal surfaces, abraded skin Followed by attachment to host cells and multiplication Dissemination to regional nodes and internal organs
Natural nature of untreated syphilis.adapted from Rein MF, Musher DM. Late syphilis.in: Rein MF (ed). Atlas of infectious Disease, Vol V: Sexually Transmitted Diseases. New York: Current Medicine, 1995:10.1-10.13
Secondary Syphilis Widespread manifestation of disseminated T. pallidum Occurs within weeks to months ffg chancre or simultaneously especially with HIV Can last for weeks/months Relapses can be seen in up to 25%
Annular
Papulosquamous
Corymbose
Localised Syphilids
Condylomata lata
Moth eaten alopecia
Co-existence of syphilis & HIV Several atypical manifestations False Seronegativity Higher RPR titre Rapid progression to neurosyphilis Relapse despite adequate treatment Failure of therapy esp. second line therapies
Immune Reconstitution Inflammatory Syndrome and Syphilis IRIS has been reported in association with broad range of skin infections, inflammatory disorders and neoplasms 2006, C. Hardwick et al 1 st case reported Several other cases reported since then
Feb 2015 Diagnosed HIV CD4 count 185 cells/mm3 Viral Load 100200 copies/ml ARV therapy initiated
May 2015 Biopsy in keeping with Syphilis RPR screen Reactive RPR titre 1024 CD4 count- 231 cells/mm3 Viral load 804 copies/ml Secondary syphilis manifesting as IRIS
Investigations Darkfield Microscopy Skin biopsy -H&E -special studies-immunohistochemical stain for T. pallidum -Wartin Starry -PCR
Investigations Serology -Non-Treponemal & Treponemal tests Non-Treponemal : VDRL, RPR, TRUST Treponemal : TPHA,MHA,TPPA,FTA-ABS assay,
Management No vaccine to prevent infection Timely diagnosis and treatment imperative Education, contact tracing Since breakthrough in 1943 by Maloney et al Benzathine Penicillin gold standard treatment T. pallidum remained exquisitely sensitive
So what does this actually mean? Start using 2 nd line therapies - Doxy/tetracycline, Ceftriaxone, Azithromycin 2 nd line therapies, although proven effective, still don t have enough supporting data Further fuel biggest public health threat- Antibiotic Resistance!! Longer duration Rx-? Poor and non-compliance Azithromycin reported cases of resistance due to gene mutations
Conclusion Syphilis continues to present challenges to global health Increasing numbers of syphilis, despite previously available penicillin therapy With current global shortage: High index of suspicion Education of health care providers Prevention late syphilis that is associated with high morbidity and as well mortality if CNS and CVS involvement
References Eccleston K, et al: Primary syphilis. Int J STD & AIDS 2008; 19:25 French P: Syphilis. Br Med J 2007; 334:143 Nessa K, et al: Field evaluation of simple rapid test in the diagnosis of syphilis. Int J STD & AIDS 2008; 19:316 Harper K, et al: On the orugins of treponematoses, a phylogenetic approach. PLoS Neg Trop Dis 2008; 2:e148 Centres for Disease Control and Prevention: Syphilis testing algorithims using treponemal tests for initial screening- four laboratories. New York City,2005-2006. MMWR 2008; 57:872 Lewis DA, Young H: Syphilis. Sex Transm Infect 2006; 82:iv13 Stoner B: Current controversies in the management of adult syphilis. Clin Inf Dis 2007; 44:S130 Singh A et al. Syphilis: Review with Emphasis on Clinical, Epidemiologic, and some Biologic Features. Clin Mic Rev 1999; 187:289 L.V.Stamm:Syphilis:Re-emergence of an old foe.microcell2016;vol3no.9
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