Correspondence
Primary herpes simplex infection with genital and extra-genital lesions mimicking disseminated gonococcal disease DOI: 10.1111/bjd.13183 DEAR EDITOR, Genital herpes (GH) remains one of the most widespread sexually transmitted infections (STIs) worldwide and its prevalence is currently rising in the female population of developed countries.1 However, a majority of physicians consider primary GH as an unusual entity in daily practice.2 Clinically atypical or misleading presentations may be an important cause of this underdiagnosis.2,3 We present a 27 year-old immunocompetent woman who was admitted to the emergency department with a 4-day history of fever, abdominal pain, polyarthralgia and mild pharyngitis, along with the progressive appearance of painful cutaneous lesions on her wrists, thighs and ankles for the previous 48 h. The symptoms began during menses and 5 days after unprotected sex with a casual partner. The patient complained about dyspareunia and slight vaginal bleeding after intercourse during the previous year, but there was no history of previous GH or other STIs. No drug use or medication intake were reported and her medical history was otherwise irrelevant. Physical examination revealed a temperature of 39 °C, three small vulvar erosions clustered on the inner part of the right major labia (Fig. 1) and bilateral inguinal lymphadenopathies. Gynaecological exam reported the presence of a diffuse and easily bleeding cervical inflammation with prominent purulent exudate. She also presented eight isolated painful umbilicated pustules on an ill-defined erythematous base, scattered along the four extremities (Fig. 2). Painful joints included knees and wrists but there was no sign of true arthritis. Basic laboratory exams found a transient moderate pancytopenia. A conventional scan failed to identify an organic origin of her abdominal pain. Pregnancy test, blood cultures and all serological studies, including HIV testing and serum herpes simplex virus (HSV) type 1 and HSV type 2 antibodies, were negative. Gram staining, bacterial cultures and polymerase chain reaction (PCR) test for Neisseria gonorrhoeae and Chlamydia trachomatis revealed no organism on the samples from swabs of the cervix, pharynx and rectum. A punchbiopsy of a cutaneous lesion showed superficial necrosis without cytopathic changes. There was neither leukocytoclasis nor perivascular inflammatory infiltrate. Specific immunohistochemistry staining for HSV gave negative results. Finally, HSV-2 was isolated by culture © 2014 British Association of Dermatologists
Fig 1. Unilateral superficial vulvar erosions.
both from genital erosions and cutaneous pustules. Clinical and microbiological clearance was obtained after five days of intravenous acyclovir (5 mg per kg every 8 h). No new cutaneous lesions were observed during her hospitalization and the pre-existing pustules healed without scarring or residual hyperpigmentation within the first three days of treatment. Crops of clustered genital erosions and vesicles are the classical clinical features of GH. Primary infections are usually more severe and may be accompanied by an important systemic involvement with fever, myalgia and meningeal signs. It is also well known that atypical presentations such as large, painful and refractory ulcers, visceral manifestations or disseminated cutaneous lesions may appear in patients with underlying immunosuppression.4 However, many physicians do not suspect this diagnosis when young and healthy patients present with clinically atypical primary GH, such as symptomatic herpetic cervicitis and distant extragenital cutaneous lesions.2,3 A diffuse, purulent and nonulcerated cervicitis beginning with menses in a sexually active young woman, who also complains of pharyngeal symptoms, is described as strongly indicative of a gonococcal origin.5 On the other hand, a mild erosive cervicitis frequently accompanied by extensive vulvar vesiculation and disproportionate dysuria should make us rule out a herpetic aetiology.1,3 Although isolated cervical HSV (without or with minimal vulvar lesions) is generally thought to be a silent STI,5 the first episode of herpetic cervicitis may be clinically indistinguishable from Neisseria gonorrhoeae or Chlamydia trachomatis infections, as we have seen in our patient. British Journal of Dermatology (2014)
1
2 Correspondence
(a)
(b)
(c)
(d)
(e)
(f)
Fig 2. Scattered pustules with surrounding erythema and a pinpoint vesicle in the centre (a, b, c), involving both lower and upper extremities: wrists (d), thighs (e) and ankles (f).
According to published data, extragenital cutaneous involvement associated with GH varies from 9% to 61%.2,6 The highest incidence has been reported among women and during true primary episodes (those with previous negative HSV antibodies).7 Clinical findings usually consist of grouped vesicles and erosions on an erythematous base, resembling the classical morphology of herpetic lesions.2,6,7 Even though any part of the body may be affected, nongenital lesions among immunocompetent patients with GH are usually described as involving limited and serologically related areas: the lower body (buttocks and thigh) in patients with HSV-2 GH, and the upper body (perioral regions) in those with HSV-1 GH.2,6 This serologically determined distribution and the characteristic herpetiformis clustering seem to be caused by direct inoculation of the virus during close contact or by intraneuronal spreading.1,6 However, the clinical presentation of extragenital lesions observed in our immunocompetent patient (disseminated pustules) differs significantly from this pattern and might be better explained by haematogenous spreading. The isolation of HSV from blood samples has been well documented in patients with systemic immunosuppression or conditions related to a higher risk of dissemination, such as pregnancy.8 Recently, Harel et al.9 demonstrated the presence of viraemia in 34% of immunocompetent children with primary British Journal of Dermatology (2014)
HSV-1 gingivostomatitis. Whether herpetic viraemia correlates with a clinical dissemination in otherwise healthy patients with primary GH remains unknown. Our case reinforces the hypothesis that haematogenous spreading during primary GH might play an important pathogenic role not only in immunossuppresed individuals but also in systemic manifestations of immunocompetent patients.10 Although fever, arthralgia and distant skin lesions represent the typical picture of disseminated gonococcal infection, dermatologists should bear in mind that primary GH may resemble this clinical appearance. Dermatology Department, 12 de Octubre University Hospital, Madrid, Spain E-mail: [email protected]
L . M A R O N~ A S - J I M EN E Z D. MENIS A . M . D E L G A D O - M AR Q U E Z C. ZARCO-OLIVO F.J. ORTIZ DE FRUTOS
References 1 Schiffer JT, Corey L. New concepts in understanding genital herpes. Curr Infect Dis Rep 2009; 11:457–64. © 2014 British Association of Dermatologists
Correspondence 3 2 Lautenschlager S, Eichmann A. The heterogeneous clinical spectrum of genital herpes. Dermatology 2001; 202:211–19. 3 Uusk€ ula A, Raukas E. Atypical genital herpes: report of five cases. Scand J Infect Dis 2004; 36:37–9. 4 Tyring SK, Carlton SS, Evans T. Herpes. Atypical clinical manifestations. Dermatol Clin 1998; 16:783–8. 5 Lusk MJ, Konecny P. Cervicitis: a review. Curr Opin Infect Dis 2008; 21:49–55. 6 Benedetti JK, Zeh J, Selke S, Corey L. Frequency and reactivation of nongenital lesions among patients with genital herpes simplex virus. Am J Med 1995; 98:237–42. 7 Corey L, Adams HG, Brown ZA, Holmes KK. Genital herpes simplex virus infections: clinical manifestations, course, and complications. Ann Intern Med 1983; 98:958–72.
© 2014 British Association of Dermatologists
8 Stanberry LR, Floyd-Reising SA, Connelly BL et al. Herpes simplex viremia: report of eight pediatric cases and review of the literature. Clin Infect Dis 1994; 18:401–7. 9 Harel L, Smetana Z, Prais D et al. Presence of viremia in patients with primary herpetic gingivostomatitis. Clin Infect Dis 2004; 39:636–40. 10 Osio A, Fremont G, Petit A et al. An unusual bipolar primary herpes simplex virus 1 infection. J Clin Virol 2008; 43:230–2. Funding sources: none. Conflicts of interest: none declared.
British Journal of Dermatology (2014)
Primary herpes simplex infection with genital and extra-genital lesions mimicking disseminated gonococcal disease DOI: 10.1111/bjd.13183 DEAR EDITOR, Genital herpes (GH) remains one of the most widespread sexually transmitted infections (STIs) worldwide and its prevalence is currently rising in the female population of developed countries.1 However, a majority of physicians consider primary GH as an unusual entity in daily practice.2 Clinically atypical or misleading presentations may be an important cause of this underdiagnosis.2,3 We present a 27 year-old immunocompetent woman who was admitted to the emergency department with a 4-day history of fever, abdominal pain, polyarthralgia and mild pharyngitis, along with the progressive appearance of painful cutaneous lesions on her wrists, thighs and ankles for the previous 48 h. The symptoms began during menses and 5 days after unprotected sex with a casual partner. The patient complained about dyspareunia and slight vaginal bleeding after intercourse during the previous year, but there was no history of previous GH or other STIs. No drug use or medication intake were reported and her medical history was otherwise irrelevant. Physical examination revealed a temperature of 39 °C, three small vulvar erosions clustered on the inner part of the right major labia (Fig. 1) and bilateral inguinal lymphadenopathies. Gynaecological exam reported the presence of a diffuse and easily bleeding cervical inflammation with prominent purulent exudate. She also presented eight isolated painful umbilicated pustules on an ill-defined erythematous base, scattered along the four extremities (Fig. 2). Painful joints included knees and wrists but there was no sign of true arthritis. Basic laboratory exams found a transient moderate pancytopenia. A conventional scan failed to identify an organic origin of her abdominal pain. Pregnancy test, blood cultures and all serological studies, including HIV testing and serum herpes simplex virus (HSV) type 1 and HSV type 2 antibodies, were negative. Gram staining, bacterial cultures and polymerase chain reaction (PCR) test for Neisseria gonorrhoeae and Chlamydia trachomatis revealed no organism on the samples from swabs of the cervix, pharynx and rectum. A punchbiopsy of a cutaneous lesion showed superficial necrosis without cytopathic changes. There was neither leukocytoclasis nor perivascular inflammatory infiltrate. Specific immunohistochemistry staining for HSV gave negative results. Finally, HSV-2 was isolated by culture © 2014 British Association of Dermatologists
Fig 1. Unilateral superficial vulvar erosions.
both from genital erosions and cutaneous pustules. Clinical and microbiological clearance was obtained after five days of intravenous acyclovir (5 mg per kg every 8 h). No new cutaneous lesions were observed during her hospitalization and the pre-existing pustules healed without scarring or residual hyperpigmentation within the first three days of treatment. Crops of clustered genital erosions and vesicles are the classical clinical features of GH. Primary infections are usually more severe and may be accompanied by an important systemic involvement with fever, myalgia and meningeal signs. It is also well known that atypical presentations such as large, painful and refractory ulcers, visceral manifestations or disseminated cutaneous lesions may appear in patients with underlying immunosuppression.4 However, many physicians do not suspect this diagnosis when young and healthy patients present with clinically atypical primary GH, such as symptomatic herpetic cervicitis and distant extragenital cutaneous lesions.2,3 A diffuse, purulent and nonulcerated cervicitis beginning with menses in a sexually active young woman, who also complains of pharyngeal symptoms, is described as strongly indicative of a gonococcal origin.5 On the other hand, a mild erosive cervicitis frequently accompanied by extensive vulvar vesiculation and disproportionate dysuria should make us rule out a herpetic aetiology.1,3 Although isolated cervical HSV (without or with minimal vulvar lesions) is generally thought to be a silent STI,5 the first episode of herpetic cervicitis may be clinically indistinguishable from Neisseria gonorrhoeae or Chlamydia trachomatis infections, as we have seen in our patient. British Journal of Dermatology (2014)
1
2 Correspondence
(a)
(b)
(c)
(d)
(e)
(f)
Fig 2. Scattered pustules with surrounding erythema and a pinpoint vesicle in the centre (a, b, c), involving both lower and upper extremities: wrists (d), thighs (e) and ankles (f).
According to published data, extragenital cutaneous involvement associated with GH varies from 9% to 61%.2,6 The highest incidence has been reported among women and during true primary episodes (those with previous negative HSV antibodies).7 Clinical findings usually consist of grouped vesicles and erosions on an erythematous base, resembling the classical morphology of herpetic lesions.2,6,7 Even though any part of the body may be affected, nongenital lesions among immunocompetent patients with GH are usually described as involving limited and serologically related areas: the lower body (buttocks and thigh) in patients with HSV-2 GH, and the upper body (perioral regions) in those with HSV-1 GH.2,6 This serologically determined distribution and the characteristic herpetiformis clustering seem to be caused by direct inoculation of the virus during close contact or by intraneuronal spreading.1,6 However, the clinical presentation of extragenital lesions observed in our immunocompetent patient (disseminated pustules) differs significantly from this pattern and might be better explained by haematogenous spreading. The isolation of HSV from blood samples has been well documented in patients with systemic immunosuppression or conditions related to a higher risk of dissemination, such as pregnancy.8 Recently, Harel et al.9 demonstrated the presence of viraemia in 34% of immunocompetent children with primary British Journal of Dermatology (2014)
HSV-1 gingivostomatitis. Whether herpetic viraemia correlates with a clinical dissemination in otherwise healthy patients with primary GH remains unknown. Our case reinforces the hypothesis that haematogenous spreading during primary GH might play an important pathogenic role not only in immunossuppresed individuals but also in systemic manifestations of immunocompetent patients.10 Although fever, arthralgia and distant skin lesions represent the typical picture of disseminated gonococcal infection, dermatologists should bear in mind that primary GH may resemble this clinical appearance. Dermatology Department, 12 de Octubre University Hospital, Madrid, Spain E-mail: [email protected]
L . M A R O N~ A S - J I M EN E Z D. MENIS A . M . D E L G A D O - M AR Q U E Z C. ZARCO-OLIVO F.J. ORTIZ DE FRUTOS
References 1 Schiffer JT, Corey L. New concepts in understanding genital herpes. Curr Infect Dis Rep 2009; 11:457–64. © 2014 British Association of Dermatologists
Correspondence 3 2 Lautenschlager S, Eichmann A. The heterogeneous clinical spectrum of genital herpes. Dermatology 2001; 202:211–19. 3 Uusk€ ula A, Raukas E. Atypical genital herpes: report of five cases. Scand J Infect Dis 2004; 36:37–9. 4 Tyring SK, Carlton SS, Evans T. Herpes. Atypical clinical manifestations. Dermatol Clin 1998; 16:783–8. 5 Lusk MJ, Konecny P. Cervicitis: a review. Curr Opin Infect Dis 2008; 21:49–55. 6 Benedetti JK, Zeh J, Selke S, Corey L. Frequency and reactivation of nongenital lesions among patients with genital herpes simplex virus. Am J Med 1995; 98:237–42. 7 Corey L, Adams HG, Brown ZA, Holmes KK. Genital herpes simplex virus infections: clinical manifestations, course, and complications. Ann Intern Med 1983; 98:958–72.
© 2014 British Association of Dermatologists
8 Stanberry LR, Floyd-Reising SA, Connelly BL et al. Herpes simplex viremia: report of eight pediatric cases and review of the literature. Clin Infect Dis 1994; 18:401–7. 9 Harel L, Smetana Z, Prais D et al. Presence of viremia in patients with primary herpetic gingivostomatitis. Clin Infect Dis 2004; 39:636–40. 10 Osio A, Fremont G, Petit A et al. An unusual bipolar primary herpes simplex virus 1 infection. J Clin Virol 2008; 43:230–2. Funding sources: none. Conflicts of interest: none declared.
British Journal of Dermatology (2014)
