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Woman Seeks Answers After 3 Years of Painful Genital Ulcers

— Histopathology reveals a disease most often seen in young children

Last Updated January 31, 2023
MedpageToday
A photo of a woman in a gynecological chair.

A woman in her late 40s presented with painful ulcers in her groin and armpits that hadn't healed in 3 years, an Indian group reported in .

The woman explained that when the sores first appeared, they were just itchy, oozing, reddish bumps; over time, they worsened to form painful, pus-filled oozing ulcers. She had been treated with numerous courses of antibiotics, antifungals, and steroids, in both topical and pill forms, but the sores had never healed completely. Her scalp was often scaling and greasy, she added, and also had not improved with shampoos or topical steroids.

On providing a more detailed medical history, the patient noted that for the past 4 years, she has been urinating very frequently and is always thirsty, according to Keshavamurthy Vinay, MD, of Postgraduate Institute of Medical Education and Research in Chandigarh, India, and colleagues.

Clinicians performed a physical examination, which revealed multiple mobile lymph nodes in the cervical and inguinal regions that were firm, nonmatted, and nontender. The patient's liver was enlarged 2 cm below the right costal margin, they noted, and the parotid area was also enlarged bilaterally and tender on palpation.

The patient had yellowish greasy scales resembling seborrheic dermatitis on her scalp. Clinicians also noted reddened swollen bumps on the skin behind her ears and on the folds beneath her breasts.

The external genitalia were notable for deep ulcers resembling knife-cut ulcers on both left and right inguinal folds, wrote Vinay and co-authors, and similar lesions discharging yellowish pus were evident on the junction of labia majora and labia minora. The team obtained a 3.5-mm punch biopsy specimen from the perimeter of an ulcer on one of the groin folds.

"Histopathological examination revealed a dense infiltration of lower epidermis and upper dermis by atypical Langerhans cells," Vinay and colleagues reported. "These cells were large with a characteristic coffee bean-shaped grooved vesicular nuclei and moderate amphophilic cytoplasm." Staining results were positive for CD1a and Langerin. Based on these findings, clinicians diagnosed the patient with Langerhans cell histiocytosis (LCH).

Routine blood tests returned normal findings, and were negative for HLA-B51 and enzyme-linked immunosorbent assay for Epstein-Barr virus IgM and IgG. A PET scan revealed "fluorodeoxyglucose-avid involvement of bone marrow, skeletal system (in the form of lytic lesions), lungs, bilateral salivary glands, mucosae, and skin of flexural areas and scalp," the group noted.

The female patient had pituitary involvement in the form of diabetes insipidus confirmed on contrast-enhanced MRI of sella, which revealed absence of posterior pituitary bright spot.

Clinicians arrived at the final diagnosis of multisystem LCH with organ dysfunction of low-risk type.

Discussion

Clinicians reporting this case of LCH, a disorder of clonal proliferation of Langerhans cells, noted that the disease rarely occurs in adults. tend to be affected more commonly, especially those between ages 1 to 3 years.

"Apart from the typical cutaneous features such as recalcitrant seborrheic dermatitis, candidal intertrigo, and eczematous eruption in the flexures, as observed in this patient, nonhealing ulcers in the perineal areas and external genitalia can be a presenting feature of LCH," Vinay's group wrote.

Adults with LCH tend to present with multisystem disease, most commonly involving the bones. While dermatologic manifestations occur in as many as 50% of cases, has been observed to be uncommon among reported cases of adult LCH.

LCH involving the skin, bones, lymph nodes, lungs, or pituitary gland is classified as low-risk disease, while LCH with dysfunction of the hematopoietic system, liver, or spleen is classified as high-risk multisystem LCH.

Case authors described several differential diagnoses they considered. They described the patient's genital lesions being similar to those seen in Crohn's disease metastases. Metastatic Crohn's disease may present with similar fissures, swelling, and deep knife-cut ulcers in the vulva and perineal area, separated from the underlying gastrointestinal pathology.

In contrast to LCH, however, Crohn's disease would have histological evidence of noncaseating granulomas on examination and evidence that the gastrointestinal tract was involved, authors said.

They also considered Behcet disease, known to involve genital ulcers, which ultimately did not fit the bill because histopathological examination would have shown neutrophilic infiltration of the dermis, leukocytoclastic vasculitis, and thrombosis in tandem with systemic thrombotic and vasculitic manifestations, uveitis, and positive pathergy test.

Other conditions that may cause painful genital or perineal ulcers include cutaneous T-cell lymphomas (CTCLs) such as extranodal natural killer/T-cell lymphoma and primary anaplastic large-cell lymphoma, the authors noted, adding that the epidermotropic infiltrates observed in this patient may also occur in CTCLs. "Immunohistochemistry for T-cell-specific and other markers such as CD56 or CD30 may be required to rule out a CTCL in LCH cases with prominent epidermotropism," they wrote.

Because genital lesions often resemble symptoms of other multisystem inflammatory disorders, Vinay and colleagues urged early histopathological diagnosis to differentiate ulcerative manifestations of LCH from other diseases that can present with genital ulcers.

"This will allow for appropriate screening for systemic involvement and early initiation of appropriate therapy," they said.

Disclosures

Case authors reported no conflicts of interest.

Primary Source

JAMA Dermatology

Anubha D, et al "Nonhealing genital ulcers as clue to a multisystem disease" JAMA Dermatol 2023; DOI: 10.1001/jamadermatol.2022.5863.