César Bimbi¹, Georgia Kyriakou², Piotr Brzezinski³, Uwe Wollina⁴

¹ Dermatologia Clinica & Laser, Porto Alegre, Brazil
² Department of Dermatology, University General Hospital of Patras, Patras, Greece
³ Department of Physiotherapy and Medical Emergency, Faculty of Health Sciences, Pomeranian Academy, Slupsk, Poland
⁴ Department of Dermatology and Allergology, Municipal Hospital Dresden – Academic Teaching Hospital, Dresden, Germany

Introduction

Darier disease (DD), otherwise known as Darier-White disease or keratosis follicularis, is a rare inherited autosomal dominant genodermatosis characterized by loss of epidermal cells adherence (acantholysis) and aberrant epidermal keratinization (dyskeratosis). The clinical features include the presence of greasy malodorous hyperkeratotic papules grouped in seborrheic areas, appearing in late childhood to early adulthood [1]. Palmar pits, nail abnormalities and mucous membrane changes are additional findings. DD is often exacerbated by sun exposure, perspiration, stress, friction and medications [2-3].

Mutations in ATP2A2 gene, encoding a Ca2+ pump, cause defective formation of the tonofilament-desmosome complex resulting in acantholysis and supra-basal lacunae (clefting) [3]. Penetrance is high but clinical presentation is variable and most patients manage to lead a relatively normal life. DD is a chronic unremitting condition, and its severity fluctuates over time [2, 6]. Clinical variants include hypertrophic and bullous subtypes, while linear unilateral-segmental forms may also occur. In these patients there may be overlap among different clinical subtypes of the disease on different body areas. There are also strikingly rarer and unique cases of extreme phenotypes reported in the medical literature displaying extensive skin involvement associated with neuropsychiatric abnormalities [4]. Erythrodermic variants have been documented [5].

Patients with Darier’s disease have a life expectancy equal to the general population. However, colonization of the fissures and disruption of the epidermal barrier secondary to acantholysis are predisposing factors for serious viral and bacterial infections, and septicemia with fatal outcomes has been reported in DD patients [6, 7].

Case report

An otherwise healthy 40-year-old Caucasian woman with an established diagnosis of Darier’s disease, living in a remote Brazilian village, consulted our teledermatology service during the pandemic period. Since the time of the diagnosis at the age of 8, she had been treated intermittently with various topical corticosteroids along with topical retinoids and short courses of oral acitretin at the dosage of 10 mg q.d. Although the disease had not evolved for decades, a rapid deterioration was detected during the last two weeks. During this period the patient experienced symptoms of fever, chills, malaise, tachycardia, and unbearable pain accompanied by widespread facial clusters of umbilicated vesicles and pustules evolving into crusted skin erosions (Fig. 1). Erythroderma dominated the clinical picture, and a widespread desquamation was observed all over her body skin surface (Fig. 2). Warty vegetating malodorous plaques evolved in the genital area.

Fig. 1: widespread umbilicated vesiculopustules on the head progressing to punched-out coalescent erosions that formed a large, denuded area on the face.

Given the dramatic clinical presentation and the accompanying symptomatology, the patient was advised to be urgently admitted to the local hospital. IgM antibodies to HSV in the serum were positive. She was administered intravenous aciclovir (10 mg/kg/q8h) along with broad-spectrum antibiotics following serum culture. An increase of the acitretin dosage to 30 mg q.d. in a continuous fashion following infection resolution, along with topical keratolytic ointments and mupirocin application, was also suggested. Substantial symptom amelioration followed by significant clinical improvement was observed a few days later (Figure 3).

Fig. 2: Well-demarcated and widespread erythematous erosions dominated the clinical picture all over skin surface area.

Discussion

Kaposi’s varicelliform eruption (KVE) also known as eczema herpeticum constitutes a potential life-threatening dermatologic emergency. Herpes simplex virus (type 1 or 2) can spread from asymptomatic shedding from the oral mucosa and infect the impaired epidermis. Darier patients have been reported to carry higher risks of KVE [8]. In a 20-year retrospective analysis of 79 patients with Darier’s disease, eleven (14%) developed KVE, of whom 45% required hospitalization. Patients with severe forms of Darier disease were more likely to be hospitalized. Hence, systemic aciclovir is justified to prevent a devastating course, and antibiotics may become necessary depending on blood culture [9].

Fig. 3: Substantial symptom amelioration followed by significant clinical improvement was observed a few days after initiation of treatment.

KVE with possible serious secondary infection by multiple microorganisms resulting in septicemia, as in our case, is a less known complication of Darier’s disease. A dermatologist is necessary in situations like these as general practitioners may not have the clinical expertise to make this diagnosis. When the eye is affected, an ophthalmologist must be contacted.

The aim of the report is to increase awareness of the condition and emphasize the need for correct and timely diagnosis as well as prompt treatment with antiviral therapy along with wide-spectrum antibiotics since the infection may have fulminant outcomes. Diagnosis of KVE is made primarily on clinical findings. Skin biopsy, or detection of viral DNA by Polymerase Chain Reaction may be helpful in doubtful cases. Scraping the vesicles floor followed by Wright-Giemsa stain (Tzanck smear) is a rapid, easily applicable, and inexpensive method to demonstrate multinucleated giant cells [9, 10].

Prompt treatment of KVE prevent and/ or minimize complications. Intravenous aciclovir (10 mg/kg/q8h) combined with broad-spectrum antibiotics following serum culture, along with topical keratolytic ointments and mupirocin application are valuable treatments for these cases. Darier patients, especially those with severe forms, must be aware of the importance of avoiding intense sun exposure which may trigger this infection.

Conflict of Interest: None to declare.

Funding: The author(s) received no specific funding for this work.

The authors certify that they have obtained all appropriate patient consent forms, in which the patients have given consent for images and other clinical information to be included in the journal.