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Section 2. Medical science
Anoshina Tatiana Nikolaevna, PhD, Assistant of the Department of Obstetrics, Gynecology and Reproduction, Shupik National Medical Academy of Postgraduate Education, Kyiv, Ukraine E-mail: [email protected]
Clinical course of genital herpes in HIV-infected pregnant women
Abstract: HIV-infected pregnant women have severe manifestations of the clinical course of genital herpes, which was accompanied by a characteristic colpo- and vulvoscopic picture (inflammatory background, herpes vesicles, ulcers, erosion, hyperemia, apparent edema, serous-inflammatory discharge, multi-vessels, severe reaction on acetic acid, rough epithelial relief with micropapillary needled like outgrowths of the connective tissue). It was demonstrated the expediency of express diagnostics (Tzanck sample, Schiller test). There were specific for HSV cytologic manifestations: increased sizes of nuclei in epithelial cells, form of watch-glass, multinucleated cells, muddy unstructured chromatin. In 40.0% of patients the Cowdry bodies were found. In 40.0% of HIV-infected patients a tendency to recurrence of HSV was revealed.
Keywords: HIV, herpes, pregnancy, colposcopy, cytology.
Introduction. The course of pregnancy in HIV- primary infection and 12 — with the reactivation). Ten
infected women is often accompanied by fetal growth retardation, low birth weight, fetal death, premature delivery, ill-timed discharge of amniotic fluid [1]. It is believed that these complications occur more frequently as a result of HIV-associated infections, but not HIV [2; 3].
Numerous studies demonstrated that in HIV-infect-ed women the herpes virus detected with high rates in the structure of associated infections. It is known that herpes viruses may activate HIV gene in provirus stage and there is cofactors for progress of HIV infection to AIDS [4; 5].
The clinical manifestations of herpes simplex virus infection (HSV) in HIV-positive patients are more aggressive, with frequent relapses and systemic lesions, and this compromised the course of underlying disease [6].
Objective: To characterize the clinical course of genital herpes infections in HIV-infected pregnant women.
Materials and methods. The evidences of the study of specific Ig M, Ig G and IgG avidity are demonstrated the activity of virus herpes simplex virus (HSV) type 2 in 24 of the 50 infected women (8 women — primary infection, 16 — reactivation process). In 18 women observed a typical clinical picture of genital herpes (6 — with the
of these women have the first clinical episodes.
HSV-2 diagnosis was based on the identified changes of genitals using colposcopic techniques with accounting the data of cytological investigations. Colposcopy (vulvoscopy) is conducted with 10-20x magnifications. Simple colposcopy means the examination of the mucous membrane without diagnostic solutions. Further extended colposcopy performed with a 3-percent solution of acetic acid (acetic acid test). Tzanck sample and Schiller test with Lugol were used. Cytological and direct microscopic study was performed according to the conventional techniques. Staining of preparations was performed according to Papanicolaou, Papengeym, and Romanovsky-Giemsa.
Results and discussion. We observed the following stages of the clinical form of HSV-2 primary episodes: 1 — incubation period (2-7 days); 2 — initial-prodromal (minimally symptomatic) — 1-2 days; 3 — culmination (multi-symptomatic period of rash), symptomatic — from 3 to 14 days; 4 — regressive (re-parative) — from 2 to 10 days; 5 — subclinical period (recovery) — to relapse.
As can be seen from Table 1, the initial phase was characterized by small number of symptoms, mainly
complaints on itching (70.0%); 20.0% of women felt a tingling, 20.0% — pain, 20.0% — edema, 10.0% — redness. In 10.0% there was an increase of whole body temperature.
The appearance of herpetic vesicles with clear contents in all women (in 80.0% — the ulcers with sharp margins and flat bottoms) indicated on the culminating stage, that in all women accompanied by pain, redness, purulent and serous discharges, positivity of Tzanck sam-
ples. The vast majority of patients mentioned the tingling and itching, 20.0% — myalgia, 20.0% — increasing of regional lymph nodes, 40.0% — rise of temperature. Almost in all (90.0%) the vessels with response on diagnostic solution, bleeding vessels, and negative Schiller test were observed. In 60.0% was noted a rough, granular, lumpy relief of mucous, in 10.0% — micropapillary papillae (needle-like hyperplasia of the connective tissue), acetowhite epithelium.
Tablel - Clinical diagnostic manifestations of genital herpes in HIV-infected pregnant women according to the period of process (2 — initial; 3 — culmination; 4 — reparative; 5 — subclinical),%
Diagnostic manifestations Period of herpes process
2 3 4 5
Tingling 20,0 60,0 10,0 -
Redness 10,0 100,0 60,0 20,0
Itching 70,0 30,0 20,0 10,0
Pain 40,0 100,0 40,0 20,0
Development of herpetic vesicles — 100,0 40,0 10,0
Ulcers with sharp margins and flat bottom - 80,0 30,0 10,0
Myalgia - 20,0 10,0 -
Enlarged of regional lymph nodes - 20,0 10,0 -
Rise of temperature 10,0 40,0 20,0 10,0
Edema 20,0 90,0 30,0 10,0
Purulent and serous discharges - 100,0 20,0 10,0
Vessels with response on diagnostic solution - 90,0 40,0 10,0
Bleeding vessels - 90,0 30,0 10,0
Rough, grainy, and lumpy relief - 60,0 40,0 30,0
Micropapillary papillae - 10,0 40,0 20,0
Acetowhite epithelium, - 10,0 10,0 50,0
Sheeler Test in affected area positive - - 20,0 40,0
slightly positive 20,0 10,0 50,0 10,0
negative 70,0 90,0 30,0 30,0
Tzanck sample positive - 100,0 70,0 10,0
negative - - 30,0 90,0
In the reparative period, the number of vesicles decreased (40.0%), being replaced with hyperpigmentation crusts, accompanied by pain; in 40.0% with a decrease of complaints on tingling (10.0%) and pruritus (20.0%). At the transition to the subclinical stage (30 hours from the onset of clinical signs) in HIV-infected pregnant women observed some clinical diagnostic manifestations of genital herpes.
The initial process on the vulvar and cervical mucosa was characterized by redness of varying intensity, moderate edema, presence of translucent vesicles with different sizes, a small number of vessels, reaction to acetic acid (constriction — dilatation), mild severity of pain syndrome. Cytologically, the period was characterized by a large number of white blood cells with prevailing of polynuclear cells, in a presence of macrophages, lym-
phocytes, and histiocytes. The epithelium has dystrophic changes. It was noted the isolated double-nucleated cells. The viral cytopathic typical for herpes changes in this period not be detected (Table 2).
The culmination period — the number of vesicles increases, it size enlarges, part of the vesicles dissilientes with forming of ulcers on their place, true erosion, inflammation background, hyperemia, apparent edema, serous-inflammatory discharges, multi-vessels, pronounced reaction on acetic acid (rapid constriction — dilatation), severe pain. Cytologically, the HSV-specific changes were developed on inflammatory background (large amount of neutrophilic, eosinophilic and lym-phoid elements, including plasma cells, histiocytes, and cells of fibroblastic family). The nuclei of epithelial cells considerably enlarged. The large number of multinucle-
ated cells which are formed not as a result of mitotic division, but at adhesion and stratification of nuclei are present. Typical features of nuclei: turbid (opaque) unstructured chromatin; nuclei looked as if through frosted glass; grain structure of chromatin is absent, the pres-
ence of regional (marginal) chromatin. The swelling of the nucleus, the nucleus are looked as «watch glass». In 40.0% of patients the Cowdry bodies (nuclear bodies with a light halo) were detected, that was apparent sign of herpes virus infection.
Table 2 - Cytological features of genital herpes in HIV-infected pregnant women according to the period of process (2 - initial; 3 - culmination; 4 - reparative; 5 - subclinical),%
Cytological features Period of herpes process
2 3 4 5
Increased nuclei 10,0 90,0 20,0 10,0
Loosening nuclei 10,0 90,0 30,0 10,0
Changes in nuclei forms (polymorphism) 10,0 60,0 20,0 -
Hyperchromatosis of nuclei - 30,0 20,0 10,0
Swelling of nuclei 10,0 80,0 40,0 20,0
Multinucleated cells 20,0 90,0 30,0 20,0
Margination of thickened chromatin - 70,0 40,0 10,0
Erased, dirty, and grayish chromatin 10,0 100,0 40,0 20,0
Unstructured chromatin, appearance as «watch glass» 10,0 90,0 40,0 20,0
Structured chromatin 30,0 - 30,0 60,0
Muddy chromatin structure 20,0 100,0 70,0 30,0
Intranuclear inclusions with illumination area (Cowdry bodies) 10,0 40,0 10,0 10,0
Enlarged cytoplasm 60,0 30,0 20,0
Vacuolated cytoplasm 30,0 20,0 -
Packed cytoplasm 20,0 10,0 10,0
Fuzzy contour of cytoplasm 40,0 20,0 10,0
In reparative period, the majority of patients had a relief or absence of pain, reduction of congestion, little or no blood vessels, lack of response to acetic acid, absence of vesicles, ulcer epithelialization without rough relief, isolated small ulcers, and lack of needled-like reaction of connective tissue. In some HIV-positive patients (40.0%) are still noted the presence of ulcers, red color, uneven reliefwith raised portions, lesions, rough epithelial reliefwith micropapillary needled-like outgrowths of the connective tissue.
Cytologically, this period characterized by a small amount of leukocytes, most of which are presented by macrophage and lymphoid elements. In the majority of patients herpes-specific viral cytopathic changes in this period were not observed, reparative changes in the cells were mild. In 40% of patients preserved the cytological background (typical for herpetic changes), namely: the presence of white blood cells, small number of macrophages, isolated double- and multinucleated cells with a weak violation of chromatin structure, blurred chroma-tin, pronounced reparative changes in cells.
Subclinical period (at a month after the onset of symptoms) in most patients vulvo- and colposcopically
characterized by a flat uniform relief of the mucosa surface, whitish and slightly red coloring, and absence of granular raised acetowhite erosive vesical areas. In 10.0% of patients the slightly grainy relief was detected, that can be explained by normal teratogenesis of the vulva mucous membrane. In some patients (40.0%) colposcopy and vulvoscopy characterized by a motlier picture, coloring was diverse: from white to red, the surface of some areas was raised, micropapillary, round-granular; in 10.0% the small vesicles in the 1st cervix uteri zone were observed by colposcopy.
Cytologically, this period in the majority of patients characterized by the following picture: squamous epithelium without structure, cytoplasm and nuclei disturbing, well-structured chromatin in the nuclei, the absence of double- and multinucleated cells, the vulva epithelium without hyper-, para- and dyskeratosis, isolated leukocytes. However, in some women it was noted an increased number of white blood cells, the dystrophic and degenerative changes of epithelium, presence of isolated double-nucleated cells with a weak structuring of chromatin, some clouding of the nuclei, which is typical for the recurrence risk.
Conclusions. Thus, this study found that HIV-positive pregnant women have severe manifestations ofthe clinical course of genital herpes (pain, redness, herpetic vesicles, purulent and serous discharges, in 20.0% — an enlarging of regional lymph nodes, in 40.0% — fever), which was accompanied by a characteristic colpo- and vulvoscopic picture (the presence of vesicleing, ulceration, erosion, hyperemia, apparent edema, serous-inflammatory discharges, multi-vessels, intense reaction on acetic acid — fast constriction-dilatation, rough epithelial relief with micropapillary needled-like outgrowths ofthe connective tissue on the inflammatory background). The expediency
of express-diagnostics (at the culmination period 100% patients have a positive Tzanck test and negative or slightly positive Schiller test) was established.
The diagnosis of genital herpes confirmed by HSV-specific cytological manifestations: nuclei of epithelial cells have much larger sizes, looked as watch-glass, mul-tinucleated cells, turbid (opaque) unstructured chromatin). In 40.0% of patients Cowdry bodies were found, that is also typical for HSV.
In HIV-infected patients revealed a tendency to recur (in 40.0% observed the colposcopic and cytological signs of relapse at the end of 1 month).
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