Rare Overlap of 2 Autoinflammatory Keratinization Diseases Observed in Single Lesion

A recent case study published in the Journal of Cutaneous Pathology¹ illustrated the coexistence of hidradenitis suppurativa (HS) and porokeratosis palmaris et plantaris disseminata (PPPD) in a patient, both of which are now categorized under the umbrella of autoinflammatory keratinization diseases (AIKDs).

The case underscores the challenges in managing these complex, genetically-influenced conditions, particularly when traditional treatments fail to provide sufficient relief.

Hidradenitis suppurativa of axilla | Image Credit: © Te Whatu Ora; DermNet

Background and Methods

The term AIKDs was coined by Akiyama et al. to describe a group of skin disorders characterized by genetic mutations that result in an innate immune system malfunction, leading to epidermal inflammation and hyperkeratosis.²

Initial AIKDs included diseases like generalized pustular psoriasis and palmoplantar pustulosis. Over time, HS and porokeratosis were also recognized as part of the AIKD spectrum due to their shared pathophysiological traits, such as inflammation within the epidermis and upper dermis.³

The patient in this case study was a 52-year-old male with a history of atopic dermatitis, who presented with a 10-year history of painful nodules in the axillary and genital regions consistent with HS, alongside a 2-year history of hyperkeratotic rashes suggestive of PPPD. Researchers conducted and described a detailed clinical and histopathological investigation to examine the progression and potential overlap of these conditions. Biopsies confirmed the presence of PPPD, while molecular testing identified no atypical infectious causes.

Findings

Upon presentation, the patient exhibited interconnected sinus tracts with active drainage, scarring, and thick, verrucous plaques across typical HS sites such as the axillae and groin, as well as nontraditional areas like the face and extremities. These plaques continued to worsen despite treatment with adalimumab, which led to the discontinuation of the drug after 7 months.

A second biopsy revealed invasive squamous cell carcinoma (SCC) arising within a porokeratosis lesion, which was subsequently treated with Mohs surgery.

Histopathological analysis of the patient's hyperkeratotic plaques confirmed the presence of PPPD, a rare variant of porokeratosis that often involves the palms and soles. The lesions were also noted to exhibit hypertrophic porokeratosis involving cystic hair follicles, a hallmark of PPPD. The treatment regimen, initially based on adalimumab, was deemed inadequate, and a more aggressive approach involving triple therapy with infliximab, acitretin, and dapsone was initiated. Although dapsone was eventually discontinued due to anemia, the patient showed improvement with the remaining treatments.

Sixteen months after starting triple therapy, the patient showed noticeable improvement, with reduced drainage from HS lesions and some regression of the hyperkeratotic plaques. The addition of deucravacitinib, a newer agent, further contributed to symptom management.

Conclusions

This case emphasizes the complexities in diagnosing and managing AIKDs, particularly when 2 conditions overlap, as seen with HS and PPPD. The patient's response to treatment highlights the challenges clinicians face when conventional therapies fail, necessitating a more tailored, multi-pronged therapeutic approach.

However, despite the patient's improvement, the case demonstrates the limitations of current treatment options for such complex diseases, especially when the underlying genetic causes remain unclear.

"To our knowledge, ours is the first reported case of squamous cell carcinoma arising in a porokeratosis in a patient with concurrent hidradenitis suppurativa," according to case report authors Rogers et al. "More studies aimed at better understanding the disease pathogenesis and underlying genetic factors behind AIKDs may help expand the treatment arsenal for refractory, challenging cases."

Furthermore, while the patient’s response to treatment was encouraging, the recurrence of porokeratosis and the development of SCC in the lesion highlight the ongoing need for vigilant monitoring. As the field of AIKDs continues to evolve, the recognition of diseases like HS and PPPD within this framework may lead to new insights into their genetic underpinnings and treatment strategies.

References

1. Rogers MC, Ash M, Hernandez A, Hosler GA. A patient with concurrent hidradenitis suppurativa and porokeratosis palmaris et plantaris disseminata: case report and review of autoinflammatory keratinization diseases. J Cutan Pathol. Published online January 3, 2025. doi:10.1111/cup.14774
2. Akiyama M, Takeichi T, McGrath JA, and Sugiura K. Autoinflammatory keratinization diseases. J Allergy Clin Immunol. 140, no. 6 (2017): 1545–1547.
3. Blicharz L, Czuwara J, Rudnicka L, Torrelo A. Autoinflammatory keratinization diseases-the concept, pathophysiology, and clinical implications. Clin Rev Allergy Immunol. 2023;65(3):377-402. doi:10.1007/s12016-023-08971-3