Buschke–Fischer–Brauer Keratoderma: A Case Report of a Rare Skin Disorder

ABSTRACT

Buschke–Fischer–Brauer keratoderma is a rare autosomal dominant disorder presenting as hyperkeratotic lesions on the palms and soles. Diagnosis requires clinical and histopathological evaluation. Management is symptomatic with keratolytics like salicylic acid and urea. Early recognition and ongoing care improve the quality of life for patients with this chronic condition.

1. Introduction

Palmoplantar Keratoderma (PPK) is a broad term for a group of heterogeneous diseases characterized by hyperkeratosis of the palms and soles [1]. These conditions can be either acquired or inherited. Hereditary PPK can be classified into three main categories: diffuse, focal, and punctate PPK (PPPK) [2, 3]. The punctate type is further divided into PPK type I (Buschke‐Fischer‐Braur), type II (Spiny Keratoderma), and type III (Acrokeratoelastoidosis, AKE), all of which are characterized by numerous small hyperkeratotic papules on areas of mechanical pressure [4, 5]. The prevalence is estimated to be around 1.17/100,000. Although the exact etiology remains unclear, both genetic and environmental factors are thought to contribute. PPPK follows an autosomal dominant inheritance pattern and is associated with loci on chromosomes 15q22, 15q24, and 8q24.13–8q24.21 [6, 7]. Recent studies have further identified mutations in specific genes, most notably AAGAB and COL14A1, as contributing to disease pathogenesis [5, 8]. In this report, we present the clinical and histopathological characteristics of a patient diagnosed with type I PPPK.

2. Case History/Examination

A 44‐year‐old woman presented with a 15‐year history of multiple asymptomatic, small, firm keratotic lesions on her palms and soles. The patient reported a positive family history, with both her father and grandmother having similar lesions. Her past medical history and systemic review were unremarkable. On examination, numerous brownish, pitted hyperkeratotic papules coalesced into larger verrucous plaques on both palms and soles (Figures 1 and 2). No other lesions were observed on the body, and her nails, hair, and mucosal membranes were unaffected.

FIGURE 1.

Hyperkeratotic papules and plaques on the palms.

FIGURE 2.

Hyperkeratotic papules and plaques on the soles.

The patient underwent routine laboratory tests, including a complete blood count, liver enzymes, creatinine, urea, electrolytes, and a chest X‐ray. All results were within normal limits. Genetic analysis was not performed as it is unavailable in our country.

Two skin biopsies were obtained from hyperkeratotic lesions. Histopathological examination revealed massive hyperkeratosis, hypergranulosis, acanthosis, and papillomatosis, with a dermal lymphocytic infiltrate (Figure 3).

FIGURE 3.

Hematoxylin and eosin‐stained microscopic images of the lesion. (A) Low‐power view showing hyperkeratosis (40×); (B) Acanthosis and papillomatosis (40×); (C) Dermal lymphocytic infiltrate (100×); (D) Hypergranulosis (200×).

3. Differential Diagnosis, Investigations, and Treatment

The patient's clinical features and histopathology findings ruled out other conditions such as psoriasis, lichen planus, and verruca vulgaris. The presence of hyperkeratosis, acanthosis, and papillomatosis was consistent with Buschke–Fischer–Brauer Keratoderma. The patient was prescribed a topical regimen consisting of salicylic acid (10 g), urea (10 g), sulfur (2 g), and Vaseline (20 g), along with urea 40% cream.

4. Outcome and Follow‐Up

The patient experienced partial relief, although the lesions persisted.

5. Discussion

PPPK, specifically Buschke–Fischer–Brauer disease, is a rare genetic disorder characterized by hyperkeratotic lesions on the palms and soles. The condition follows an autosomal dominant inheritance pattern and typically presents in early adulthood. Due to its rarity, there is limited literature available, with only a few case reports [1, 2]. Although Buschke–Fischer–Brauer disease has long been considered a benign hereditary keratoderma, recent advances have clarified its genetic basis. Two distinct subtypes have been described. Type 1A results from mutations in the AAGAB gene, mapped to chromosome 15q22–q24. The AAGAB gene encodes the alpha‐ and gamma‐adaptin binding protein, which plays a crucial role in clathrin‐mediated endocytosis and regulation of receptor tyrosine kinase turnover in keratinocytes. Loss‐of‐function mutations in AAGAB lead to defective endocytic trafficking and aberrant signaling, thereby contributing to abnormal keratinization. In contrast, type 1B has been linked to mutations in the COL14A1 gene on chromosome 8q24.12–q24.13, which encodes collagen type XIV, a protein involved in extracellular matrix organization and dermal–epidermal structural integrity. These findings highlight the heterogeneity of the disease and suggest that altered intracellular trafficking and extracellular matrix interactions may represent two distinct pathogenic mechanisms underlying punctate keratoderma [5, 8]. The clinical presentation in our patient, with asymptomatic, firm keratotic lesions and family history, is consistent with the hereditary nature of PPPK.

A combination of clinical and histopathological evaluation is essential for diagnosing PPPK. In our patient, brownish pitted papules and plaques on the palms and soles, without nail, hair, or mucosal involvement, were characteristic. Histopathology revealed hyperkeratosis, hypergranulosis, acanthosis, and papillomatosis, aligning with descriptions in the literature [3]. Differential diagnoses, including other forms of palmoplantar keratoderma, psoriasis, lichen planus, and verruca vulgaris, were excluded based on clinical and histological findings [5, 6]. Although Buschke–Fischer–Brauer keratoderma is generally considered a benign condition, cases have been reported describing its association with an increased risk of malignancies, including colon adenocarcinoma, prostate cancer, breast cancer, and metastatic non‐small cell lung cancer, as well as neurological disorders, nail dystrophies, psoriasis, and keratosis pilaris [4].

Treatment options for PPPK are primarily symptomatic, aimed at reducing lesions and improving quality of life. Common treatments include keratolytics, such as salicylic acid and urea, and systemic retinoids in more severe cases. Although our patient experienced partial improvement, the persistence of the lesions is common in PPPK, highlighting the chronic nature of the disease [5]. The chronic and recurrent nature of PPPK, coupled with its significant impact on the patient's daily activities and quality of life, necessitates ongoing management and patient education [7]. This includes regular use of topical treatments, periodic debridement, and patient counseling about the genetic nature of the disease and its long‐term management strategies.

6. Conclusion

Buschke–Fischer–Brauer keratoderma is a rare but distinct form of PPPK that requires careful diagnosis and ongoing management. Our case contributes to the limited body of literature and emphasizes the importance of recognizing this condition, particularly in patients with a positive family history and characteristic lesions.

Author Contributions

Dyala Sayed Ahmad: conceptualization, data curation, formal analysis, investigation, methodology, resources, writing – original draft, writing – review and editing. Rim Nasser: conceptualization, data curation, formal analysis, investigation, methodology, resources, writing – original draft, writing – review and editing. Moatasem Hussein Al‐janabi: project administration, validation, visualization. Fouz Hassan: supervision, validation, visualization.

Ethics Statement

The authors have nothing to report.

Consent

Written consent for the publication of patient photographs and medical information was obtained.

Conflicts of Interest

The authors declare no conflicts of interest.

Ahmad D. S., Nasser R., Al‐janabi M. H., and Hassan F., “Buschke–Fischer–Brauer Keratoderma: A Case Report of a Rare Skin Disorder,” Clinical Case Reports 13, no. 10 (2025): e71021, 10.1002/ccr3.71021.

Data Availability Statement

The authors have nothing to report.