Case report

International Journal of STD & AIDS

2019, Vol. 30(13) 1340–1343
Herpetiform aphthous genital ulcers ! The Author(s) 2019
Article reuse guidelines:
misdiagnosed as herpes genitalis in sagepub.com/journals-permissions
DOI: 10.1177/0956462419870672
a young male and their effective journals.sagepub.com/home/std

response to colchicine therapy

Snigdha Saxena , Sidharth Tandon, Kabir Sardana and

Sonali Bajaj

Abstract
Genital ulceration can be a source of tremendous stress to the patient, as well as to the family members, and poses a
difficult and sensitive diagnostic conundrum for the clinician. Cultural taboos and social stigmas related with the disease
often result in the clinician not believing the patient’s version of history and basing the diagnosis entirely upon the clinical
picture, aided by diagnostic tests. The clinicians should keep in mind that sexually transmitted infections (STIs), which
can cause genital ulceration are very common, but there is a long list of non-sexually acquired causes of genital
ulceration, which can lead to a diagnostic dilemma, and these should be considered before labelling the patient as
suffering from a STI. We present a rare case of herpetiform genital aphthous ulcers mimicking herpes genitalis and
chancroid, which was misdiagnosed repeatedly, and their effective response to treatment with colchicine on subsequent
identification of the correct diagnosis.

Keywords
Bacterial disease, chancroid (Haemophilus ducreyi), diagnosis, Herpes simplex virus, other, treatment, viral disease
Date received: 13 June 2019; accepted: 28 July 2019

Background
ulcers. Herpetiform aphthae are 1–3 mm in size, occur
Genital ulcers/erosions could be caused by a number of in clusters that may coalesce, are negative for HSV, and
causes not related to sexually transmitted infections heal over 1–4 weeks.4 Constant presence of three or
(STIs). Misdiagnosed commonly as STIs or mistaken more oral ulcers or recurrent oral and genital aphthae
for sexual abuse in children, they induce significant is defined as complex aphthosis.5
emotional distress in the patient/family. Lipschutz in Persistent multiple erosions are a common
1913 reported non-venereal, acutely developing, presentation in an STD clinic, which may be due to
vulvar ulcers in young virginal women, the ulcus herpes genitalis, HSV being a common STI. Clinicians
vulvae acutum, without a clear infectious source. should however be aware that non-STIs (Epstein Barr
Acute genital ulcers or Lipschutz ulcers occur predom- virus, Cytomegalovirus, Paratyphoid, Influenza A, and
inantly in females and can be found in women of any Mycoplasma pneumoniae) and other non-infectious
age, including those who are sexually active.1 Often causes, viz. idiopathic aphthosis can lead to acute genital
preceded by prodromal symptoms, viz. fatigue, anorex- ulceration.2
ia, and low-grade fever, they present as one or multiple
ulcers, usually on the medial surface of labia minora
and less commonly on labia majora, perineum, and Dr Ram Manohar Lohia Hospital and Postgraduate Institute of Medical
lower vagina. Accompanied sometimes by oral apthous Education and Research, New Delhi, India
ulcers, acute genital/oral ulceration may be recurrent in
Corresponding author:
few cases.2,3 Snigdha Saxena, Dr Ram Manohar Lohia Hospital and Postgraduate
Aphthous ulcers on mucous membranes are classi- Institute of Medical Education and Research, New Delhi, India.
fied into minor, major, and herpetiform aphthous Email: snigdhasaxena8@gmail.com
Saxena et al. 1341

Herein, we describe a young sexually inactive male Investigations

adult, who was misdiagnosed as herpes genitalis on two
A Tzanck smear from ulcers base did not show multi-
occasions and treated ineffectively with antiviral drugs,
nucleated giant cells, and Gram stain showed neutrophils.
but a judicious examination, history, and investigations
Human immunodeficiency virus serology, VDRL
revealed the rare “herpetiform” variant of aphthous
and TPHA, HBsAg, anti-HCV antibodies, HSV types
ulceration, which responded to therapy with colchicine.
1 and 2 serology (IgG and IgM), and polymerase chain
reaction from ulcer swabs for HSV types 1 and 2 were
Case presentation negative. Pathergy test was negative.
A 19-year-old male patient, presented with chief com- Serum vitamin B12 was found to be low (180 pg/mL;
plaints of painful ulcerations over glans penis, persist- reference range 230–931 pg/mL), while serum folate
ing for three weeks. Lesions were preceded by burning was within range (2.85 ng/mL; reference range 2.8–
sensation, which was followed by a reddish, raised 20 ng/mL).
lesion approximately 0.5  0.5 cm in size, that pro-
gressed to form multiple small erosions (Figure 1(a)). Differential diagnosis
Additionally, a solitary painful ulcer was present on
A differential diagnosis of herpetiform genital aphtho-
scrotal skin. This was the first episode of erosions
sis and chancroid was considered.
and ulcers and onset was accompanied by fever, head- In addition to classical presentation of chancroid,
ache, and generalized myalgia. many clinical variations are seen including a dwarf
Patient had earlier consulted two dermatologists, variety, which presents as one or more herpetiform
who diagnosed it as a case of herpes genitalis and ulcerations.6
treated him empirically with weekly courses of valacy- Lack of bleeding in the genital ulcers and absence of
clovir (1 g once daily), but the lesions persisted. bubo directed us to exclude chancroid and diagnose it
On examination, the patient was afebrile. Oral as a case of herpetiform genital aphthosis.
mucosa was unaffected and there were no other extra-
genital cutaneous lesions or history of such manifesta-
tions. Abdominal examination was normal with no Treatment
organomegaly. Genital lesions were akin to chancroidal The patient was initiated on tablet colchicine 0.5 mg
ulcers, with multiple tender superficial punctate ulcers at three times daily. In view of associated vitamin B12
12 o’clock position over glans penis (Figure 1(a)). There deficiency, he was also started on tablet cyanocobala-
was no bleeding on manipulation, regional lymph nodes mine 15 mcg twice daily, along with cyanocobalamine
were non-palpable, and no other mucosa was involved. injections 1000 mcg IM, once daily for 10 days.
Repeated enquiry revealed that patient was sexually
inactive and strict vegetarian by diet. There was no his-
tory of red eye episodes, joint pains, burning micturi- Outcome and follow-up
tion, and urethral discharge. No history of similar After commencement of colchicine, by 10th day ulcer-
complaints in the past or in family members was present. ation had completely resolved leaving behind atrophic

Figure 1. (a) Multiple grouped ulcers with erythematous halo and necrotic base present over the glans penis. (b) Areas of atrophic
scarring present at the site of healed ulcers after starting colchicine therapy.
1342 International Journal of STD & AIDS 30(13)

scars (Figure 1(b)). The patient on his own stopped Laboratory investigations ruled out an STI.
colchicine after one month, with prompt recurrence Chancroid was a possible diagnosis, but lack of bleed-
of lesions, but responded well on re-starting the drug. ing and absence of bubo led us to consider aphthous
Colchicine was reduced to a twice daily dose after a ulcers, a diagnosis of exclusion.
month and continued at this dose for two months. Incidence of primary genital aphthosis is extremely
The patient continued to improve and remained ulcer low, indicated by paucity of reports in literature.
free. On repeat testing, vitamin B12 and folic acid levels Primary aphthous ulcers of genitalia are largely seen
were normal. Patient is under follow-up for more than in females, with almost total lack of publications
a year and there is no report of recurrence of lesions involving male genitalia. Huppert et al.9 reported a
till date. fairly large series of primary aphthous ulcers in young
women. In males notably, genital aphthous ulcers
tend to occur often on the scrotum. In a retrospective
Discussion study at a large children’s hospital spanning 10 years,
Leading causes of genital ulcers differ worldwide, with only 12 cases of acute idiopathic genital aphthosis
a high incidence of some STIs, viz. chancroid in the were observed, and all were girls younger than
developing countries.7 Standard protocols for investi- 18 years, indicative of a tilted sex ratio (fema-
gation of genital ulcers, adapted to the prevalent STIs les  males).10 A close mimicker is HSV, but in
in a country/region, are critically important. immunocompetent patients it presents only as ero-
In case of genital ulcers, though it is essential to rule sions rather than ulcers seen in aphthosis.11
out STIs, non-STIs and non-infectious causes consti- Herpetiform aphthosis is rarer in a study of 120
tute a much larger group (Table 1) and are most often cases of recurrent aphthous stomatitis, none had her-
misdiagnosed.3,8 petiform oral ulceration.12
In our case, ulcers persistence and non-responsiveness Mild mucocutaneous aphthous ulcers are usually
to antivirals was an indicator to look beyond herpes treated with topical corticosteroids, local anaesthetics,
genitalis. Biopsy of acute short lasting ulcers causes tetracycline, sucralfate, and tacrolimus. In more severe/
additional discomfort to patient and is not usually help- frequent attacks, systemic colchicine, pentoxifylline,
ful, displaying non-specific vasculitic changes. dapsone, and corticosteroids are reported to be
Due to psychological impact of STIs, diagnosis of useful. Refractory cases may require thalidomide, aza-
non-STIs, viz. Epstein Barr virus (EBV) as cause of thioprine, interferon-a, and TNF-a antagonists.8
genital ulcers greatly relieves the patient/family. Besides, It is important to investigate dietary history of
primary infection with EBV is self-limiting and seldom patients with aphthous ulcers, as nutritional deficien-
relapses. We did not investigate for non-STIs in our cies (iron, vitamin B12, folate) may lead to reversible
patient because of rarity of their occurrence in our geo- genital aphthosis.
graphical region. The mainstay of therapy in our case was colchicine.
The unique anti-inflammatory action of colchicine is due
Table 1. Causes of non-sexually transmitted genital ulcers. to impairment of neutrophil extravasation/chemotaxis
and suppression of NLRP3 inflammasome activation.13,14
Cause Disease
In some patients colchicine can cause painful gastro-
Infection Epstein Barr virus, cytomegalovirus, intestinal symptoms or diarrhea, and long-term use in
paratyphoid, influenza A, mycoplas- young males may lead to infertility. Monitoring during
ma pneumoniae long-term colchicine therapy should include complete
Immune mediated Behçet’s syndrome, Reiter’s syndrome, blood count and liver function tests.15
mouth and genital ulceration with To conclude, in cases with persistent genital
inflamed cartilage syndrome
ulceration, herpetiform aphthous ulcers though rare
(MAGIC syndrome)
Nutritional deficiency Iron, B12 and folatea
and mostly seen in females should be considered.
Dermatological Sweet’s syndrome, erythema multi- Important clues for their differentiation from HSV
forme, fixed drug reaction, bullous infection are the presence of ulcers as opposed to ero-
skin disorders, erosive lichen planus sions, depending on the size of lesions their healing
Gastrointestinal Crohn’s disease with scarring, and ulcers on the scrotum. Colchicine
Malignancy Erythroplasia of Queyrat, squamous cell is an effective first line therapy for herpetiform aph-
carcinoma, basal cell carcinoma, thosis, which can be maintained long term if needed,
extra mammary Paget’s disease with regular monitoring and follow-up. In case of pro-
Idiopathic Aphthous ulcers
longed colchicine treatment requirement, however, an
a
Genital ulceration not reported or very rare. alternative diagnosis should be explored.
Saxena et al. 1343

Declaration of conflicting interests therapeutic ladder from topicals to thalidomide. J Am

Acad Dermatol 2005; 52: 500–508.
The authors declared no potential conflicts of interest with
6. Brown TJ, Yen-Moore A and Tyring SK. An overview of
respect to the research, authorship, and/or publication of sexually transmitted diseases. Part I. J Am Acad Dermatol
this article. 1999; 41: 511–532.
7. Lewis DA. Chancroid: clinical manifestations, diagnosis,
Funding and management. Sex Transm Infect 2003; 79: 68–71.
8. Keogan MT. Clinical immunology review series: an
The authors received no financial support for the research, approach to the patient with recurrent orogenital ulcera-
authorship, and/or publication of this article. tion, including Behcet’s syndrome. Clin Immunol 2009;
156: 1–11.
Informed consent 9. Huppert JS, Gerber MA, Deitch HR, et al. Vulvar ulcers
in young females: a manifestation of aphthosis. J Pediatr
Written informed consent for patient information and images
Adolesc Gynecol 2006; 19: 195–204.
to be published was provided by the patient.
10. Rosman IS, Berk DR, Bayliss SJ, et al. Acute genital
ulcers in nonsexually active young girls: case series,
ORCID iD review of the literature, and evaluation and management
Snigdha Saxena https://orcid.org/0000-0002-9665-7853 recommendations. Pediatr Dermatol 2012; 29: 147–153.
11. Chugh S, Garg VK, Sarkar R, et al. Clinico-epidemio-
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