A 45-year-old man presented to the dermatology office complaining of a pruritic rash on his neck, chest, abdomen, and upper back. The rash had been present since the patient was 20, intermittently flaring and causing severe pruritus. For the past two weeks, it had become increasingly bothersome.
The patient described the rash as “greasy” brown plaques diffusely scattered on his body. The rash on his neck was the most bothersome, and the patient felt an uncontrollable need to scratch that area.
Since it first developed 25 years ago, he had used OTC hydrocortisone cream as needed to treat the rash. Although effective for past flares, the cream provided only minimal relief during the current episode.
The patient’s medical history included brittle nails with a worsening of nail quality in recent years. The family history revealed that the patient’s father and sister were affected by the same type of rash, which developed in adolescence for each of them, as well as brittle nails.
On physical examination, the skin was warm and moist to the touch. Flat, slightly elevated, greasy brown papules were scattered on the chest, abdomen, and upper back, with mild surrounding erythema (see Figure 1). Excoriated lesions were noted on the anterior surface of the neck, with pinpoint bleeding resulting from constant irritation. The patient’s fingernails were deformed, with longitudinal ridges and v-shaped notching of the free margin. The remainder of the physical exam was unremarkable, and review of systems was negative.
This patient’s symptoms could result from a variety of causes. Seborrheic dermatitis is a common skin condition that presents with brown plaques similar to those on the patient’s trunk. Another possible diagnosis is Grover’s disease, a rare disorder also known as transient acantholytic dermatosis, in which keratotic plaques appear on the torso and are thought to occur from trauma to sun-damaged skin. An additional consideration is Hailey-Hailey disease, a rare genetic disorder also known as benign familial pemphigus, which is characterized by red-brown plaques located predominantly on flexure surfaces.1 Skin biopsy should be performed for a definitive diagnosis.
Given the family history of a similar rash occurring in first-degree relatives and the distinct physical exam findings, the most likely diagnosis for this patient is keratosis follicularis, also known as Darier disease (DD) or Darier-White disease.
DISCUSSION
Named after Ferdinand-Jean Darier, who discovered this rare genodermatosis, DD is a rare genetic skin disorder caused by mutations of the ATP2A2 gene, located on the long arm of chromosome 12 at position 24,11.1,2 The mutation disrupts the encoding of the enzyme sarco/endoplasmic reticulum calcium-ATPase 2 (SERCA2). This enzyme is important in the transport of calcium ions across the cell membrane, and insufficient amounts lead to a defect in intracellular calcium signaling.2,3
This genetic mutation is inherited as an autosomal dominant trait with complete penetrance. DD affects men and women equally, with progressive skin signs of interfamilial and intrafamilial variability.4 Skin manifestations occur from late childhood to early adulthood and are typical during adolescence.4 Acute flare-ups can be triggered by heat, perspiration, sunlight, ultraviolet B exposure, stress, or certain medications (in particular, lithium).2 DD is not contagious.2
CLINICAL PRESENTATION
The characteristics of DD include yellow or brown, rough, firm papules that are frequently crusted. The papules often appear in seborrheic areas of the body, such as the chest, back, ears, nasolabial fold, forehead, scalp, and groin.4 The severity of expression varies from mild, with few lesions, to severe, in which the entire body is covered with disfiguring, macerated plaques emitting a strong odor. On biopsy, the histopathologic findings are typical of dyskeratosis and acantholysis.4
Fingernails (and occasionally toenails) display broad, white or red, somewhat translucent, longitudinal bands accompanied by v-shaped notching1,4,5 (see Figure 2). Such nail changes are diagnostic and occur in 92% to 95% of patients with DD.6 They may, in fact, occur in the absence of cutaneous disease. All nails may be affected, but usually only two to three are involved.6
Although uncommon in DD, white, umbilicated, or cobblestone plaques may be found on intraoral mucous membranes (ie, tongue, buccal mucosa, palate, epiglottis, pharyngeal wall, and esophagus); due to confluence, papules may mimic leukoplakia.7 Lesions may also appear on the vulva or rectum.1,5 In severe cases, the salivary glands can become blocked, and the gums can hypertrophy.5
Since epidermal and brain tissue both derive from ectoderm, pathologic processes that affect one organ system may also affect the other.8 Indeed, among patients with DD, neuropsychiatric problems—including epilepsy, learning difficulties, and schizoaffective disorder—are commonly reported.1 To confirm an association between DD and ATP2A2 mutations, Jacobsen and colleagues performed an analysis of 19 unrelated DD patients with neuropsychiatric phenotypes. They discovered evidence to support the gene’s pleiotropic effects in the brain and hypothesized that mutations in the enzyme SERCA2 correlate with these phenotypes, most specifically for mood disorders.9