Pustules in a 59-year-old Hispanic man

Abstract

A 59-year-old Hispanic man was attended at the Dermatology department with a widespread cutaneous eruption affecting all body areas. The patient reported no allergies, medication use, or history of autoimmune diseases, celiac disease, or recurrent tonsillitis. This skin condition developed after abruptly stopping a 60 mg prednisone regimen. The eruption was characterized by numerous pustules, some with a distinctive “half and half” appearance. Pustules coalesced into areas of superficial erosions, predominantly in flexural areas (Figures 1 and 2). The lesions exhibited a centrifugal spread, with pustules and erosions at the periphery and postinflammatory macules in the center. Upon resolution, the lesions left adherent fine scaling, areas of hyperpigmentation, and crusting. Histopathology findings are shown in Figures 3 and 4. Laboratory tests at the time showed normal results for complete blood count and blood chemistry, except for low levels of 25-hydroxyvitamin D (normal range: 30–100 ng/mL). A pustule was cultured, with negative result.

The pustules in our patient's eruption showed the “hypopyon sign,” which is characterized by the presence of small vesicles initially filled with clear fluid, that subsequently become turbid due to neutrophil infiltration, resulting in pus accumulation at the base of the vesicle when the patient is upright.¹

GPP is a rare, chronic, and severe inflammatory skin disorder characterized by sudden outbreaks of sterile pustules, often accompanied by systemic inflammation.² The diagnosis of GPP can be challenging due to its rarity (see Table 1 for differential diagnoses), and requires an accurate clinicopathological correlation. Histopathological findings may demonstrate slight acantholysis, classified as secondary because it follows keratinocytic injury rather than being caused strictly by desmosome damage.³ Although our main differential diagnosis were IgA pemphigus or its variants, a negative immunofluorescence would exclude them, considering direct immunofluorescence is reported to be positive in nearly all cases of IgA pemphigus.⁴ In fact, a meta-analysis found that IgA deposits were identified in 97% of the cases.⁵

In GPP, hyperactivation of the innate immune system, particularly the IL-36 axis, is predominant. An uncontrolled signalling and proinflammatory cytokine overproduction occurs either through overexpression of IL-36 agonists or by the expression of a dysfunctional IL-36R antagonist, leading to attraction of neutrophils to the epidermis, manifesting clinically as pustules.^{2, 6} Genetic studies have found pathogenic variations and mutations of IL36RN, CARD14, AP1S3, MPO, and SERPINA3 genes in patients with GPP.⁶

Topical treatments are generally discouraged in GPP due to potential irritation, with systemic treatments, including biological and nonbiological options, being preferred. Cyclosporin is favoured among nonbiological treatments due to its rapid onset of action.^{2, 6} Biological treatments targeting IL-36 pathways include Spesolimab and Imsidolimab. Spesolimab demonstrated rapid symptom control of moderate to severe GPP with a single 900 mg intravenous dose. However, it was associated with high infection and drug reaction rates.⁷ A clinical trial is ongoing to explore maintenance doses of Spesolimab in preventing flare-ups and controlling the disease.⁸ Imsidolimab showed promise in a phase II trial but requires further studies before approval.⁹ For our patient, guselkumab was initiated due to its suppression of the IL-36 proinflammatory signalling cascade, closely linked to the positive feedback loop of the IL-17/IL-23 axis. Guselkumab targets resident memory T cells (TRM), crucial in GPP treatment, as CD8+ TRMs decrease posttreatment.¹⁰

All authors provided care for the patient. All authors contributed to the conception and design of the study. Judith M. Corona-Herrera: Case design, writing, conception, revisions, and analysis. Betzabé Quiles-Martínez: Gathered data. Fanny C. López-Jiménez: Gathered data, draughted manuscript. Rebeca Palafox-Romo: Gathered data, critically revised manuscript. Salazar H. Amparo: Gathered data. Saeb-Lima Marcela: Contributed with histopathological pictures. Silvia Méndez-Flores: Case design, writing, conception, revisions, and analysis. All authors approved the final version for publication.

The authors declare no conflict of interest.

All patients in this manuscript have given written informed consent for participation in the study and the use of their deidentified, anonymized, aggregated data and their case details (including photographs) for publication. Ethical Approval: not applicable.