Lipschtz genital ulceration: a rare manifestation of paratyphoid fever

ARTICLE

Auteur(s) : Fabien PELLETIER¹, François AUBIN¹, Eve PUZENAT¹, Philippe DEPREZ¹, Dominique BLANC¹, Jean-Marie ESTAVOYER², Philippe HUMBERT¹

¹ Service de Dermatologie 1, Hôpital Saint-Jacques, 2, place Saint-Jacques, 25030 Besançon cedex, France. 
² Department of Infectious Diseases, University Hospital, Besançon, France

Article accepted on 18/02/2003

In 1913, a distinctive clinical entity of acute genital ulcer occurring in an adolescent girl with a non-venereal infectious aetiology was described by Lipschtz [1]. This entity is characterized by one or more vulvar ulcerations with spontaneous recovery. Among possible aetiologies, paratyphoid fever is very uncommon.

Observation

Two weeks after her return from a one-month trip to Kenya and Mauritius, a 25-year-old girl with no relevant past-history developed high fever (39 °C), genital ulceration and moderate abdominal pain with diarrhoea. Prior to the departure she had had a vaccination against yellow fever and had taken malaria prophylaxis. She was unmarried and denied any sexual activity during and after returning from the holiday. She did not apply topical medication or antiseptics. Furthermore, no history of similar ulceration involving oro-genital mucosae was noticed. She simultaneously experienced dysuria and vulvar pain. Abdominal palpation was sensitive. The examination of the vulva revealed a large genital ulcer on the left labium minus (Fig. 1) which developed the week before. This punched-out lesion with dark purple borders was covered with an adherent membrane. It was soft and tender. The rest of the general examination was normal. No lymphadenopathy and splenomegaly was noted and no treatment was prescribed. The white cell count was 5.4 × 10⁹ L-1 with 75% neutrophils. The haemoglobin level was 13.4 g dL-1. The platelets level was low (121 × 10⁹ L-1). The serum aspartate aminotransferase level was increased to 536 IU per liter (normal 0 to 40), as well as serum alanine aminotransferase level to 351 IU per liter (normal 5 to 50), whereas the alkaline phosphatase level and the total bilirubine were normal. The C reactive protein level was 55 mg per liter. Bacterial and virological cultures from the genital lesion were negative. Routine investigations of genital ulcer, including dark ground microscopy, gram staining, tissue smear and tzank smear, were negative. A blood smear excluded malaria. Bacterial cultures of stool specimen were also negative, as were serological tests for cytomegalovirus and brucellosis. IgG antibodies to the Epstein Barr virus (EBV) capsid (VCA) and IgG to nuclear antigen suggested serological scar. The biological investigations ruled out sexually transmitted diseases: serological tests for human immunodeficiency virus, syphilis (TPHA-VDRL and FTA Abs) and chlamydia were negative. Also antigen P24 was negative. Serological test for herpes type 1 and type 2 were positive (IgG antibodies). Four blood cultures were positive and identified Salmonella paratyphi A. Diagnosis of Lipschtz’s ulcer associated with evolutive paratyphoid fever was made, and bacteriaemia was treated with ceftriaxone injections (2 grams per day) for three days followed by oral ofloxacine (500 mg two times a day) for two weeks. All the symptoms (fever, abdominal pain, dysuria) and genital ulceration disappeared as well as the inflammatory syndrome and the liver alterations within 6 days.

Discussion

In 1913, Lipschtz described a distinctive clinical entity of acute genital ulcers occurring in adolescents, with no documented infectious aetiology [1]. The disease was characterized by acute onset, frequent fever, and multiple vulvar lesions. The lymph nodes were usually enlarged, and healing was spontaneously observed. Since Lipschutz’ description, several aetiologies have been discussed. Recently, vulvar acute ulcer has been associated with EBV infection [2-7]; four cases were associated with primary infection confirmed by positive polymerase chain reaction or cultures within the lesions. The mechanism of ulcer was not clear, and the role of EBV-infected B lymphocytes was suggested [7]. Other infectious diseases should be considered for the diagnosis of genital ulcers including herpes simplex virus infection, syphilis, chancroid, lymphogranuloma venereum, cytomegalovirus and brucellosis [2, 3]. A serological test for human immunodeficiency virus is essential. Caustic and traumatic ulcerations must also be ruled out as non infectious causes of genital ulcers (fixed drug eruptions, erythema multiformis, Stevens-Johnson syndrome, inflammatory bowel disease, aphtosis and Behçet’s syndrome).
In 1965, Berlin suggested that Lipschtz’ ulceration should also be considered as an acute symptom of typhoid fever [8]. Indeed, among five personal cases, two patients presented with fever typhoid with positive Felix-Widal serology. In addition, previous authors had already isolated Salmonella typhi in acute genital ulcers associated with vulvovaginitis [9]. To our knowledge, we report herein the second case associated with proved paratyphoid fever [10]. The mechanism of vulvar ulceration may involve the production of endotoxins by Salmonella paratyphi as for digestive ulcers occurring during paratyphoid fever. Altogether, these observations suggest that typhoid or paratyphoid fever should be included in the differential diagnosis of genital ulcerations, particularly when following a recent trip to an endemic zone. n

References

1. Lipschtz B. Uber eine eigenartige Geschwrsform des weiblichen Genitales (Ulcus vulvae acutum). Arch Dermatol Syph (Berlin) 1913; 114: 363-95.

2. Taylor S, Drake SM, Dedicoat M, Wood MJ. Genital ulcers associated with acute Epstein-Barr virus infection. Sex Transm Infect 1998; 74: 296-7.

3. Lampert A, Assier-Bonnet H, Chevallier B, Clerici T, Saiag P. Lipschtz’s genital ulceration: a manifestation of Epstein Barr virus primary infection. Br J Dermatol 1996; 135: 663-5.

4. Lawee D, Shafir MS. Solitary penile ulcer associated with infectious mononucleosis. Can Med Assoc J 1983; 129: 146-7.

5. Portnoy J, Ahronheim GA, Ghibu F, Clecner B, Joncas JH. Recovery of Epstein-Barr virus from genital ulcers. N Engl J Med 1984; 311: 966-8.

6. Sisson BA, Glick L. Genital ulceration as a presenting manifestation of infectious mononucleosis. J Pediatr Adolesc Gynecol 1998; 11: 185-7.

7. Wilson RW. Genital ulcer and Mononucleosis. Pediatr Infect Dis 1993; 12: 418.

8. Berlin C. The pathogenesis of the so-called ulcus vulvae acutum. Acta Derm Venereol 1965; 45: 221-2.

9. Roberts D, Barron S. Typhoid fever with vulvovaginitis. The Lancet 1958; 1043-4.

10. Van Joost T. An unusual case of vulvar ulcer of acute onset. Ned Tijdschr Geneeskd 1971; 115: 1080-2.