Familial Dyskeratotic Comedones: A Case Report and Literature Review

Introduction

Familial dyskeratotic comedones (FDC) is a rare autosomal dominant genodermatosis presenting generalized symmetrically scattered hyperkeratotic papules resembling comedones.¹ Its prevalence remains unknown and probably underestimated due to its benign and asymptomatic course and patients’ ignorance.² Skin lesions usually develop initially on the trunk or extremities and progressively spread to other body parts while sparing mucosal surfaces, palms, and soles.^1–4 The disease onset is typically around puberty, and its course is chronic and persistent.⁵ Here, we present a case of a 54-year-old woman with extensive FDC on her trunk and extremities since the age of 12. Besides, we further review previously published articles on 21 FDC cases from 11 separate families.

Case Presentation

A 54-year-old Thai woman visited the outpatient department with asymptomatic multiple, widespread comedone-like papules over her trunk and extremities for almost 40 years. The lesions first developed as pinpoint dark spots on her legs while she was 12 and insidiously spread to her trunk when she grew older. The lesions became comedone-like papules when fully formed. The patient occasionally had redness and mild pruritus at the lesions without any specific precipitating causes. She sometimes forcefully removed the central plug, but the lesions were later filled back. She previously received topical treatments from other hospitals with no improvement.

A review of other systems was unremarkable. Her medical history included non-alcoholic fatty liver disease, bilateral carpal tunnel syndrome, and functional dyspepsia. She had undergone a hysterectomy with oophorectomy 10 years ago due to endometrioma. She denied a history of smoking and alcohol drinking. Her mother, one sister, and two brothers had similar skin lesions, first appearing around their age of 10 and mainly located on extremities with occasional pruritus. The pedigree chart of her family is shown in Figure 1.

Figure 1 Pedigree chart of the patient (arrow indicates the proband).

Dermatological examination revealed generalized multiple discrete comedone-like hyperkeratotic brownish papules distributed symmetrically on the trunk and extremities, sparing palms and soles (Figure 2). The dermoscopic evaluation showed brownish, slightly elevated border follicular papules with central keratin plugs (Figure 3). Other systems were unremarkable except for her body mass index of 28.6, which corresponds to being overweight.

Figure 2 Clinical presentations: multiple discrete comedone-like hyperkeratotic brownish papules distributed symmetrically on the trunk (A) and extremities (B and C); close-up image of the lesions (D).

Figure 3 Dermoscopic features: brownish, slightly elevated border follicular papules with central keratin plugs (original magnification x20).

A skin biopsy was performed on a lesion on her left thigh. Histologic examination revealed cystic dilatation with keratotic follicular plugging and multiple zones of focal acantholytic dyskeratosis in the cystic epithelium (Figure 4). Based on the patient’s history, clinical characteristics, and histologic examination, a definite diagnosis of FDC was made. The patient was reassured that the disease course was benign, and inflammation could occasionally occur. She was then given 10% topical urea cream, 0.025% topical retinoic acid, and an oral antihistamine for the treatment. After 3 months, the patient reported slight improvement.

Figure 4 Histopathological findings: (A) cystic dilatation with keratotic follicular plugging (hematoxylin-eosin, original magnification x10) and (B) focal acantholytic dyskeratosis in the cystic epithelium (hematoxylin-eosin, original magnification x100).

Discussion

FDC is a rare autosomal dominant penetrance disease with unknown etiology. Its prevalence is probably underestimated due to its benign and asymptomatic nature and patients’ unawareness. It was first described by Carneiro et al in 1972 in a patient with widespread papules over the trunk and extremities, resembling open comedones.¹ Since then, to our knowledge, a few additional FDC cases have been described throughout the literature, with 21 affected individuals from 11 different families. Table 1 summarizes all previously reported FDC cases.^1–11

Table 1 Previously Reported Cases of Familial Dyskeratotic Comedones in the Literature

FDC can be suspected in a patient with the following distinctive features: (1) lesions clinically resembling comedones; (2) occurrence in family members; and (3) presence of dyskeratotic features on histology.⁶ The disease reveals an asymptomatic, noninflammatory, and refractory disease course.¹ Its onset is typically during childhood to early puberty, with a gradual increase in the number of lesions by age. Clinically, lesions are scattered symmetrically distributed over the trunk, face, scalp, and extremities with palms, soles, and mucosal surfaces sparing; however, the genital area has also been reported.⁴ Dermoscopic findings of FDC have never been reported. Brownish, slightly elevated border follicular papules with central keratin plugs were first demonstrated for FDC in this article. These described features may help differentiate FDC from its mimicking conditions.

Histopathological features of FDC include crater-like invagination or follicle-like structures filled with keratinous material that contains a mixture of parakeratotic cells and melanin. Dyskeratotic changes (increased eosinophilic keratinous cells containing vesicles with an occasionally seen eccentric nucleus and small nucleolus) of underlying 3–12 layers of epithelial cells are also observed.^1,10 Early-developed lesions may show only acanthosis and dyskeratosis in the epidermis.⁴ Acantholysis is also often seen and mostly starts at the base of stratum spinulosum.^2,3,10 Hypoplastic sebaceous glands, rudimentary follicle structures, and normal sweat glands can be observed near the lesion.^1,4 Attenuated surrounding connective tissues are found with an absence of arrector pili muscle. Perivascular lymphocytic infiltration is occasionally seen.^1,4 Electron microscopic examination of the lesions showed decreased desmosomal attachments in stratum malpighii and separation of tonofilaments from normal insertion sites at the desmosome.²

Differential diagnoses of FDC include Darier's disease, keratosis pilaris, Grover disease, and nevus comedonicus, which can all be distinguished by clinical presentations. Despite the fact that Darier disease and FDC share the histopathologic hallmark of acantholytic dyskeratosis, lesions of Darier's disease have a predilection on the seborrheic area, and nail abnormality is usually observed.^11–13 Keratosis pilaris presents follicular hyperkeratotic papules without comedone-like lesions distributed on the extensor surface of the proximal extremities. Grover disease reveals papulovesicular rash commonly presenting on the trunk with a preference on the anterior chest and upper back.^14,15 Lesions are typically spontaneously resolved within a year, and its prevalence is among Caucasians.¹⁴ Nevus comedonicus usually appears at birth, typically presenting as comedone-like lesions with lamellate keratinocytic material plugs arranged along Blaschko’s lines.^16–18 All clinical features of the above-mentioned help distinguish them from FDC.

Therapeutic options for FDC remain limited. Several reports found the disease refractory to treatment.⁵ Throughout the literature, FDC appeared ineffective with methotrexate, topical, and systemic retinoids. Some reports showed successful treatment with CO₂ laser,³ itraconazole,⁵ and repeated sun exposure.² CO₂ laser minimizes the appearance of lesions by its destructive ability, while itraconazole may help the condition by decreasing local yeast colonization.² However, the mechanism of frequent sun exposure in improving FDC is still unexplored.

Conclusion

We report a case of FDC in a Thai woman who developed since childhood with a delayed diagnosis. We also describe, for the first time, the dermoscopic features of this condition. Our report underlines the importance of disease recognition for prompt diagnosis. Despite the rarity of the disease, it could be underestimated due to its benign and asymptomatic course. Appropriate history taking and physical examination are essential to avoid unnecessary invasive diagnostic procedures that benefit patients’ management. Additionally, patients should be informed regarding disease course and treatment modalities since lesions are usually persistent and resistant to treatment.