Skin nontumor

• Autosomal dominant genodermatosis
• Clinical: greasy keratotic papules in a seborrheic distribution, nail changes and mucosal findings
• Histologic: acantholytic dyskeratosis

• 28 year old woman, 50 year old man and 60 year old woman presenting with acral hemorrhagic lesions (Actas Dermosifiliogr 2017;108:e49)
• 31 year old woman with asymptomatic acneiform papules on the face (Ann Dermatol 2011;23:S398)
• 48 year old woman with worsening of Darier disease after interferon alpha treatment (Case Rep Dermatol 2016;8:218)
• Man in his 50s with leonine face and keratotic papules all over his body, a condition present since childhood (Case of the Month #517)
• 67 year old woman with segmental Darier disease treated with doxycycline (Dermatol Online J 2018;24:13030)

• Mild disease: topical agents, including retinoids, vitamin D analogues and calcineurin inhibitors (Pediatr Dermatol 2011;28:197, J Dermatol 2010;37:718, Eur J Dermatol 2011;21:301)
• Systemic retinoids (Indian J Dermatol Venereol Leprol 2021;87:14)
• Laser ablation (Arch Dermatol 1999;135:423)
• Botulinum toxin injections (Orphanet J Rare Dis 2021;16:93)

Contributed by Michael Fitz-Henley, M.B.B.S., D.M. and Viktoryia Kazlouskaya, M.D. (Case #517)

Contributed by Jonathan D. Ho, M.B.B.S., D.Sc. and Viktoryia Kazlouskaya, M.D. (Case #517)

• Hailey-Hailey disease:
  • Intraspinous to full thickness acantholysis
  • Less prominent dyskeratosis
  • Dilapidated brick wall appearance
• Acrokeratosis verruciformis of Hopf:
  • Church spire hyperkeratosis, hypergranulosis and papillomatous epidermal hyperplasia
  • Lesions may be identical to flat topped acral papules of Darier disease (J Dermatol 2016;43:275, J Invest Dermatol 2003;120:229)
  • No acantholytic dyskeratosis seen
• Pemphigus vulgaris:
  • Suprabasal and intraspinous acantholysis without corp rond and grain formation
  • Intraepidermal, intercellular deposition of IgG/C3
• Transient acantholytic dermatosis (Grover disease):
  • May have identical histopathologic features
  • Distinction is easy based on clinical features (relapsing remitting pruritic papular eruption in middle aged to elderly males)
• Warty dyskeratoma:
  • Identical Darier type acantholytic dyskeratosis but solitary lesion
  • Tends to have distinct cup shaped epidermal invagination and very prominent villus formation (J Dermatol 2017;44:232)
• Acantholytic dyskeratotic acanthoma:
  • Darier or pemphigus type acantholytic dyskeratosis but solitary papule or nodule; rarely erythronychia (J Cutan Pathol 2007;34:494)
  • Regular acanthosis without a cup shaped invagination (Dermatol Pract Concept 2014;4:25)
• Acantholytic dermatosis of the genitocrural area:
  • Darier or Hailey-Hailey type histopathologic appearance
  • Limited to the genitocrural area
  • No other clinical features of heritable acantholytic disease
• Focal acantholytic dyskeratosis:
  • Incidental acantholytic dyskeratosis without a clinical correlate of an acantholytic condition (J Am Acad Dermatol 1998;38:243)
  • May be seen in normal skin or adjacent to a variety of benign or malignant tumors (J Am Acad Dermatol 1998;38:243)

A 35 year old man presents with a 10 year history of scaly papules on the face and chest. Biopsy reveals the findings shown in the image above. What is the most likely diagnosis?

1. Darier disease
2. Hailey-Hailey disease
3. Herpes simplex virus infection
4. Pemphigus vulgaris
5. Seborrheic dermatitis

A. Darier disease. The photomicrograph shows acantholysis with dyskeratosis (corp ronds and grains) as well as the formation of villi classically seen in Darier disease. While Hailey-Hailey disease may have acantholysis with dyskeratosis, prominent corp ronds and grains are lacking. Pemphigus has bland acantholysis and herpes simplex shows distinct viral cytopathic change. Seborrheic dermatitis is a spongiotic dermatitis.

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Reference: Darier disease

Which of the following diseases may demonstrate histopathologic features identical to Darier disease?

1. Grover disease
2. Hailey-Hailey disease
3. Inflammatory and linear verrucous epidermal nevus
4. Pemphigus foliaceus
5. Pemphigus vulgaris

A. Grover disease. Grover disease has multiple histopathologic patterns including those with Darier type histology. All other options lack typical corp rond and grain formation.

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Reference: Darier disease

Where is the abnormal protein located in Darier disease?

1. Cytoplasm
2. Endoplasmic reticulum
3. Golgi apparatus
4. Mitochondria
5. Nucleus

B. Endoplasmic reticulum. An abnormal SERCA2 protein is located in the endoplasmic reticulum and plays a role in the Ca²⁺ signaling pathway regulating cell to cell adhesion and differentiation of the epidermis (Nat Genet 1999;21:271).

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Reference: Darier disease