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Genital Ulcers Associated with Systemic Lupus Erythematosus - What are the Possible Causes? A Case Report

July 2023
European Journal of Case Reports in Internal Medicine 10(8)

DOI:10.12890/2023_003972

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CC BY-NC-ND 4.0

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Unlabelled: Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease that affects many organs. In this report, we discuss the case of a patient with SLE who presented to an out-hospital clinic, complaining of fever and pain with genital ulcers. Negative evaluations for other causes of genital ulcers, indicated these ulcers as related to SLE. This case highlights the importance of including SLE ulcers in the differential diagnosis of genital ulcers. Learning points: Determining the cause of genital ulceration is a clinical challenge, especially in sexually active individuals.Genital ulcers associated with SLE are often underdiagnosed. Any patient with a history of SLE presenting with genital discomfort and/or pain must be evaluated for genital ulcers without delay.

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European Federation of Internal Medicine

GENITAL ULCERS ASSOCIATED WITH SYSTEMIC LUPUS

ERYTHEMATOSUS – WHAT ARE THE POSSIBLE CAUSES? A

CASE REPORT

Maysoun Kudsi, Tasneem Drie, Ghina Haidar, Safaa Al-Sayed, Enas Roumieh

Rheumatology Department, Faculty of Medicine, Damascus university / Syrian Private University, Damascus, Syria

Corresponding author: Ghina Haidar e-mail: gtghinahaidar@gmail.com

Received: 06/06/2023 Accepted: 21/06/2023 Published: 29/07/2023

Conicts of Interests: The Authors declare that there are no competing interests.

Paent Consent: Consent was obtained from the patient but excluded the use of images.

This arcle is licensed under a Commons Aribuon Non-Commercial 4.0 License

How to cite this arcle: Kudsi M, Drie T, Haidar G, Al-Sayed S, Roumieh E. Genital ulcers associated with systemic lupus erythematosus – what are the possible

causes? A Case Report. EJCRIM 2023;10:doi:10.12890/2023_003972.

ABSTRACT

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease that affects many organs. In this report, we

discuss the case of a patient with SLE who presented to an out-hospital clinic, complaining of fever and pain with genital

ulcers. Negative evaluations for other causes of genital ulcers, indicated these ulcers as related to SLE. This case highlights

the importance of including SLE ulcers in the differential diagnosis of genital ulcers.

KEYWORDS

Systemic lupus erythematosus, genital ulcers, autoimmune diseases, systemic conditions

LEARNING POINTS

• Determining the cause of genital ulceration is a clinical challenge, especially in sexually active individuals.

• Genital ulcers associated with SLE are often underdiagnosed. Any patient with a history of SLE presenting with genital

discomfort and/or pain must be evaluated for genital ulcers without delay.

INTRODUCTION

Systemic lupus erythematosus (SLE) is a systemic

autoimmune condition that targets healthy organs, with a

higher incidence in females, especially of reproductive age[1].

Infection is a frequent trigger factor for SLE. Infection can

also increase morbidity and mortality in SLE patients[2]. The

differentiation of SLE are and infection in a febrile patient is

difcult, thus C-reactive protein, procalcitonin, and disease

activity markers play a role[3]. Although only a few cases of

SLE genital ulcers have been published, ruling out SLE in

patients presenting with genital ulcers is important[4]. The

precise etiology and pathogenesis of SLE remain unclear,

however, it is described as an excessive immune response

to infectious agents. Viruses, bacteria, parasites, and

fungi are thought to trigger inammation, autoantibody

production and immune-mediated tissue injury[5]. Recently,

molecular mimicry in genetically predisposed individuals

has been hypothesized to exacerbate immune responses to

self-antigens by immune mistake[6]. The rst case of genital

ulcer associated with SLE was reported by Fresko et al.[7].

We describe a case of a young female patient with SLE who

presented with a history of painful genital ulcers.

papular ulcers with well-demarcated borders. These lesions

are seen in both discoid lupus and SLE[7,11,12].

The pathophysiology of ulceration in the setting of immune

dysregulation remains largely unknown, although histologic

examination has shown inammatory inltrate, likely

involving activation of T cells, and release of tumor necrosis

factor alpha[10,11].

In establishing a differential diagnosis of the genital ulcers,

we considered sexually transmitted diseases, infections,

dermatologic diseases-related, related systemic diseases

such as Crohn’s disease (CD), malignancies, traumatic ulcers,

and idiopathic disease[12].The diagnosis of Behçet’s disease

can be condently made if there are at least three reported

episodes of mouth ulcers over the past 12 months and the

presence of two of the following symptoms: genital ulcers,

ocular manifestation, dermatologic manifestation and

positive pathergy reaction[13]. The diagnosis is made when

the patient meets the rst critera: oral ulcer with 2 of the

other 4 manifestations. Our patient did not t the criteria of

Behçet’s disease, as she had only bipolar mouth ulcers.

Lipschütz ulcer is an infrequent, self-limited, nonsexually

transmitted ulcer characterized by the rapid onset of

vulvar edema along with painful necrotic ulcerations. It

may be preceded by inuenza-like or mononucleosis-like

symptoms. In our case, we made a diagnosis of exclusion[14].

Our patient had fever, no edema in the genital ulcer, she had

been diagnosed with SLE, and she did not report any prior

symptom compatible with inuenza or mononucleosis. The

patient did not report any sexual relationship outside of

marriage. She did not t the diagnostic criteria for Crohn’s

disease[15].

Negative culture for microorganisms in genital ulcers can

exclude infection[13], as in our case. In the 2019 ACR/EULAR

criteria, ANA at a titer of ≥1:80 is a mandatory criterion. The

more specic antibodies for SLE, anti-dsDNA and anti-Sm,

are grouped in one domain and weighted equally by 6 points.

Anti-dsDNA has been found to be positive in 70-90% of SLE

patients[8,16].

Physical examination alone cannot distinguish genital ulcers

associate with lupus from vulvar ulcers associated with

CD. The only way to conrm and differentiate between

genital CD and genital SLE is via biopsy[14], the procedure we

followed.

The treatment includes non-steroidal anti-inammatory

drugs, antimalarial drugs like hydroxychloroquine,

prednisolone, immunosuppressive drugs, and biologics, in

addition to surgery in some cases[15]. Our patient had been

treated with prednisolone and hydroxychloroquine, with

a good response. An untreated ulcer could progress to

squamous cell carcinoma[11].

Romiti and colleagues[16] prescribed prednisolone in

two cases of discoid lupus erythematosus affecting the

genital area, with widespread discoid lesions on the head.

Paidi and colleagues[11] prescribed the same treatment

to a young female patient with a history of CD, idiopathic

thrombocytopenic purpura, SLE, and hypothyroidism,

CASE PRESENTATION

A 28-year-old Syrian female presented to our out-hospital

clinic in December 2021, complaining of fever and discomfort

in the genital area for 10 days. She was diagnosed with

SLE, according to the American College of Rheumatology/

European League Against Rheumatism 2019[8], as she

had fever, fatigue, malar rash, oral aphthae, arthritis,

pleuritis, and positive antinucleotides antibody (ANA). She

had been treated with 200 mg/day hydroxychloroquine

until admission. The remaining medical history was

unremarkable. No family history of SLE was reported. On

physical examination, multiple papular genital ulcers, sized

1-3 mm and well dened were found. Lymphadenopathy was

present, but no vaginal discharge or ulcers were present. The

remaining physical examination was unremarkable.

Hematologic and metabolic proles were established, as

well as a viral prole on blood and urine cultures. A vulvar

biopsy and fungal swab test were ordered. CT of the pelvis

and abdomen was ordered. The complete chemical and

metabolic panels showed thrombocytopenia, with a platelet

level of 93,000/µl (150,000-400,000/µl). Anti-double-

stranded DNA (Anti dsDNA) antibody was 6UI/ml (normal).

Urinalysis was notable for 1+ hematuria and 1+ proteinuria.

Blood and urine cultures were negative for viruses. The

COVID-19 test was negative. Serologies for herpes virus

1 and 2, Epstein-Barr virus, cytomegalovirus, mycoplasma

pneumonia, parvovirus B19, toxoplasmosis, rubella,

hepatitis, human immunodeciency virus, and syphilis were

negative. Bacterial vaginosis, gonorrhea, chlamydia, and

trichomoniasis were ruled out. The fungal swab test was

negative. Abdomen and pelvis CT were normal. A genital

ulcer biopsy showed irregular acanthosis in the epidermis,

ulceration, and lymphocyte inltrations, with brinoid

necrosis of the vessel wall, in the dermis. No granuloma

was seen. We decided against immunouorescence testing

due to its high costs. Other causes of genital ulcers being

ruled out, these ulcers were considered related to SLE, as

one of its mucosal involvement. The patient was treated

with 70 mg/day (1 mg/kg) prednisolone, continuing on 200

mg/day hydroxychloroquine. No antibiotic was prescribed.

Improvement started after 2 days, and the ulcers were

healed after 15 days. The prednisolone dose was eventually

tapered to 5 mg/week. After 3 months, she was doing well,

until the time of writing. Our case was submitted on the

research registry database under UIN 8837.

DISCUSSION

SLE usually involves organs, including the skin[1]. Cutaneous

manifestations are many and of wide spectrum[9]. In most

cases, skin lesions in SLE occur in sun-exposed areas[10].

Mucosal involvement is frequently manifested in lupus as

ulcers in the mouth, less frequently in the nose and throat

and rarely in the genital area[11]. Behçet’s disease presenting

as genital ulcer was excluded in our patient as she had the

diagnostic criteria of SLE[8].

SLE genital involvement presented as small–medium size,

presenting with recurrent chronic diarrhea, perianal ulcers,

the passage of blood in stools, and anal pain.

The novelty of our case is that the genital ulcers were due

to SLE, without a superimposed infection, or other diseases

such as CD. The lesions responded well to Epstein-Barr and

hydroxychloroquine, without using immunosuppressant

drugs.

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Pancytopenia as a first presentation of late-onset SLE; a case report

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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting multiple organ systems. In this report, we discuss the case of a patient with a history of idiopathic thrombocytopenic purpura (ITP), hypothyroidism, SLE, and Crohn's disease (CD) who presented to the emergency room with fever, burning micturition, abdominal pain, and perineal ulcers. Upon subsequent treatment for urinary tract infections (UTI) and negative evaluations for an infectious cause of genital ulcers like sexually transmitted diseases, the etiology of ulcers was found to be SLE. This case report highlights the importance of including SLE ulcers in the differential diagnosis when an SLE patient presents with genital ulcers and the importance of ruling out an SLE vs. infection or non-infection as the cause of ulcers in a former SLE patient.

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The diagnosis of genital ulcers remains a challenge in clinical practice. Lipschütz ulcer is a non-sexually transmitted rare and, probably, underdiagnosed condition, characterized by the sudden onset of vulvar edema along with painful necrotic ulcerations. Despite its unknown incidence, this seems to be an uncommon entity, with sparse cases reported in the literature. We report the case of an 11-year-old girl who presented at the emergency department with vulvar ulcers. She denied any sexual intercourse. The investigation excluded sexually transmitted infections, so, knowledge of different etiologies of non-venereal ulcers became essential. The differential diagnoses are extensive and include inflammatory processes, drug reactions, trauma, and malignant tumors. Lipschütz ulcer is a diagnosis of exclusion. With the presentation of this case report, the authors aim to describe the etiology, clinical course, and outcomes of this rare disease, to allow differential diagnosis of genital ulceration.

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Background The diagnosis of Behçet disease (BD) is challenging in many cases. The purpose of this study was to describe the clinical characteristics of patients at a referral BD clinic. Methods In a retrospective study, we collected data from patients at a national referral Behçet clinic from November 2018–August 2019. A BD diagnosis was confirmed (BD group) or ruled out (Non-BD group), and the two groups were compared for differences. Results A total of 238 patients satisfied the inclusion criteria. Forty patients (16.8%) were finally diagnosed with BD. Ocular and genital lesions were significantly more prevalent in the BD group. A positive pathergy test and HLA-B51 were also significantly more common in BD. However, oral lesions, articular involvement, and gastrointestinal manifestations were similar between groups. Also, patients with BD were significantly more likely to have multi-organ (≥2 organ systems) involvement. Conclusions Being the first study to evaluate the clinical characteristics of patients who are visited at a referral BD clinic and are believed to have a high probability of Behçet, the results of this study are important from an epidemiological standpoint. Also, the findings of this study could be used by referral Behçet clinics, which evaluate and diagnose patients with a high pretest probability and atypical presentations of BD on a daily basis. The alternative diagnoses established in this study could be used as the list of the most common differential diagnoses for Behçet’s disease.

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Autoimmune disorders are characterized as a condition in which the host's immune system mistakenly attacks itself. These disorders cause the immune system to cause a systemic reaction by attacking multiple organs or may be localized to attacking one specific organ, such as the skin. The exact mechanism of such autoimmune conditions is not well understood; however, the presumed mechanism tends to vary amongst the disorders. Autoimmune diseases present with a clear gender bias with a greater prevalence amongst women, occurring at a rate of 2 to 1. Many autoimmune disorders tend to affect women during periods of extensive stress, such as pregnancy, or during a great hormonal change. A far greater number of women are affected every year with autoimmune diseases, leading to researchers attempting to identify the underlying factors, which could be responsible for this disparity. Autoimmune disorders occur as a result of multiple factors as some disorders may be genetic, while others are sporadic. Throughout this review, various hypotheses are explored that provide insight into the increased susceptibility of autoimmune disorders within women.

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The majority of patients with systemic lupus erythematosus (SLE) have cutaneous manifestations at some point in their disease. The skin findings in lupus erythematosus are classified as lupus-specific or lupus-nonspecific based on histopathologic findings. Lupus-specific skin diseases include chronic cutaneous lupus erythematosus, subacute cutaneous lupus erythematosus, and acute cutaneous lupus erythematosus. There are subsets of skin lesions within each group and the likelihood of associated SLE varies amongst them. Lupus nonspecific lesions are more common in patients with SLE and tend to coincide with active systemic disease. Lupus nonspecific lesions may be seen as a feature of another disease process, including other connective tissue diseases. It is important for the rheumatologist to be familiar with the spectrum of cutaneous disease in lupus erythematosus to help prognosticate the likelihood of systemic disease and ensure patients receive timely dermatologic care with the goal of controlling disease activity to prevent damage.

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Michelle A. Roett

Genital ulcers may be located on the vagina, penis, and anorectal or perineal areas and may be infectious or noninfectious. Herpes simplex virus is the most common cause of genital ulcers in the United States. A diagnosis of genital herpes simplex virus infection is made through physical examination and observation of genital lesions. The 2015 Centers for Disease Control and Prevention sexually transmitted disease guidelines provide strategies for the management of patients with genital ulcer disease. Specific testing includes a polymerase chain reaction test for herpes simplex virus; syphilis serology and darkfield microscopy or a direct fluorescent antibody test for Treponema pallidum; and/or culture for Haemophilus ducreyi in settings where chancroid is highly prevalent. Rarely, cases of Epstein-Barr virus may present with genital ulcers. Syphilis and chancroid cause genital ulcers and are mandatory reportable diseases to the local health department. In some cases, no pathogen is identified. It is important to consider noninfectious etiologies such as sexual trauma, psoriasis, Behçet syndrome, and fixed drug eruptions. Genital ulcers are symptomatic by definition, and the U.S. Preventive Services Task Force recommends screening for syphilis infection for those at risk, early screening for syphilis infection in all pregnant women, and against routine serologic screening for genital herpes simplex virus infection in asymptomatic adolescents and adults, including those who are pregnant.

Genital Ulcers Associated with Systemic Lupus Erythematosus - What are the Possible Causes? A Case Report

Abstract

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