A new case series shows rapid remission in men with treatment-resistant pustular genital psoriasis, highlighting a potential alternative to biologics.
Genital pustular psoriasis is a rare and diagnostically challenging variant of psoriasis that remains under-recognised in clinical practice, say researchers.
Their new retrospective case series published in JEADV Clinical Practice presents compelling evidence supporting the use of apremilast, an oral phosphodiesterase-4 (PDE4) inhibitor, as a viable treatment option in male patients with this difficult-to-manage and treatment-resistant condition.
“Genital pustular psoriasis is a rare and often underdiagnosed condition that can significantly affect both physical comfort and quality of life, often leading to psychological and sexual dysfunction,” the researchers wrote.
“This subtype of psoriasis presents unique diagnostic and therapeutic challenges, as it is frequently unresponsive to conventional topical treatments, necessitating the use of systemic therapies.
“Exclusive genital psoriasis is found in only 2%−5% of psoriasis patients, and pustular involvement is even more exceptional.”
Apremilast targets the inflammatory pathways central to psoriasis by reducing pro-inflammatory cytokines.
Previous studies have demonstrated the effectiveness of apremilast in treating challenging cases, such as plaque psoriasis in special areas, genital psoriasis or palmoplantar pustular psoriasis, indicating its potential for other refractory forms of the condition.
This short case series included six men aged 21 to 47 years, who presented with persistent, recurrent circinate balanitis or balanoposthitis localised to the glans penis or the glans and prepuce.
Histopathological findings showed intraepidermal neutrophilic micro-abscesses and parakeratosis – features suggestive of pustular psoriasis, although fully formed pustules were often absent.
Each patient had undergone comprehensive diagnostic evaluation to rule out sexually transmitted infections and reactive arthritis.
All tests, including bacterial, viral, mycological swabs and syphilis serology, returned negative, and no patient exhibited systemic symptoms of reactive arthritis or extragenital psoriatic involvement.
All six patients had failed multiple standard treatments, including potent topical corticosteroids, tacrolimus, acitretin, methotrexate, and ciclosporin. These therapeutic limitations, coupled with the sensitivity of the genital area and the psychological impact of the condition, posed significant clinical management challenges, the researchers said.
While biologic therapies such as ixekizumab were known to be effective for genital psoriasis, they were often inaccessible to patients with limited or localised disease, highlighting a critical therapeutic gap, they said.
Patients in the study were started on apremilast following a standard six-day titration schedule, aiming for a maintenance dose of 30mg twice daily. One patient required a reduction to 30mg once daily due to migraines, but all patients tolerated the treatment well. Follow-up periods ranged from one to three months.
All six patients achieved complete clinical remission within this timeframe. Adverse effects were minimal and self-limiting, with mild diarrhea being the most frequently reported symptom. No patients required additional therapies, and none developed new psoriatic lesions or psoriatic arthritis during follow-up.
The authors emphasised the importance of clinicopathologic correlation, especially in genital psoriasis where the histological presentation may be subtle and clinical features such as ring-shaped (circinate) lesions could provide critical diagnostic clues.
Given the inflammatory but localised nature of the disease, apremilast’s ability to modulate proinflammatory cytokine production through PDE4 inhibition appeared to be particularly well suited for these cases, the researchers said.
While the small sample size and retrospective design of the study limit its generalisability, the consistency and speed of response in all patients point to apremilast as a highly promising treatment for refractory genital pustular psoriasis. Its favourable safety profile, ease of oral administration, and lack of serious systemic side effects made it especially appropriate for use in sensitive anatomical locations.
The researchers said their case series added to the growing body of evidence supporting the use of apremilast in psoriasis variants that were difficult to treat with conventional therapies.
They said clinicians should consider its use in appropriately selected patients, particularly those who do not meet eligibility for biologic agents or who are at risk of adverse events from traditional systemic immunosuppressants.
“Apremilast appears to be an effective and well-tolerated treatment for refractory genital psoriasis with pustular features, offering a promising therapeutic option for this rare and challenging condition,” they concluded.
“This case series suggests that apremilast can help patients achieve complete remission in a relatively short time with minimal side effects.
“In diagnosing psoriatic circinate balanitis, it is crucial to consider conditions like circinate pustular balanitis associated with Reiter’s syndrome, as well as infectious causes such as Herpes Simplex Virus, Candida albicans, group A and B streptococci and syphilis. Histology alone cannot differentiate between Reiter’s syndrome and psoriatic circinate balanitis.”
The researchers conceded the small sample size and retrospective nature of their study limited the generalisability of the findings.
“Nevertheless, increased clinical awareness and histological confirmation are essential for accurate diagnosis and effective treatment,” they wrote.
“Early recognition can help prevent misdiagnosis and inappropriate treatment, ultimately improving patient outcomes.
“This case series demonstrates that apremilast is a valuable treatment for refractory genital psoriasis with pustular features.
“Although further studies with larger cohorts and randomised controlled trials are needed to confirm the efficacy and safety of apremilast, the current findings highlight its potential for patients who have failed other treatments.”
