Clinical Challenge: Long-Term, Recurring Rash in Axillae, Groin Folds - MPR

Clinical Challenge: Long-Term, Recurring Rash in Axillae, Groin Folds

Slideshow

  • Slide

A patient, aged 60 years, presented with complaints of a rash in his armpits and groin folds that he had on-and-off since he was aged 33 years. His father and one of his sisters were affected by a similar rash.

This is a chronic condition first reported in 1939. It is caused by an autosomal dominant genetic mutation of the ATP2C1, which encodes a calcium/manganese transporter regulating calcium balance between cytosol and the Golgi apparatus.Known as Hailey-Hailey disease (HHD), after...

Submit your diagnosis to see full explanation.

This is a chronic condition first reported in 1939. It is caused by an autosomal dominant genetic mutation of the ATP2C1, which encodes a calcium/manganese transporter regulating calcium balance between cytosol and the Golgi apparatus.

Known as Hailey-Hailey disease (HHD), after the brothers who first reported it, or benign familial pemphigus.

Disruption of the calcium balance causes irregularities in adhesion between keratinocytes (skin cells). HHD has complete penetrance with variable expressivity. One-third of patients have de novo mutations and the remaining have a familial mutation.

The classic clinical presentation of this disease includes vesicular plaques or bullas usually symmetrically located in intertriginous regions and flexures such as the groin and axillae.

These vesicles may rupture causing crusting, maceration, fissuring, and may be accompanied by the presence of white lines on nails. The skin is sometimes described as appearing like wet tissue paper.

Possible complications of this disease include the development of painful fissures, or secondary infection by bacteria or viruses. Rare progression to squamous cell carcinoma has also been described.

Treatment usually involves wearing light non-restrictive clothing and minimizing sweating. Typical treatment options include topical anti-microbials and glucocorticoids, although other modalities such as immunomodulators, surgical excision, and ablation with dermabrasion or CO2 laser vaporization have resulted in improvement.

Darier disease, also known as keratosis follicularis, is caused by an autosomal dominant genetic mutation in the ATP2A2 gene, which encodes an ATPase involved in calcium transport from the cytoplasm to the endoplasmic reticulum.

As with HHD, desmosomal adhesion is disrupted due to altered calcium balance. Lesions include papules and plaques found on seborrheic areas, palmar pitting, and nail abnormalities.

Grover disease, or transient acantholytic dermatosis, is manifested by papulovesicular lesions starting initially on the trunk and spreading to extremities, often accompanied by pruritus. It may be caused by exposure to light and heat, infection, or use of certain medications.

Yasmin Qaseem, BS, is a medical student at Baylor College of Medicine.

Adam Rees, MD, a graduate of the David Geffen School of Medicine at UCLA, practices dermatology in Los Angeles.

References

  1. Buteica, E et. al. Romanian Journal of Morphology and Embryology. 2007; 48 (4): 423-426.
  2. Hunt, R et al. Dermatology Online Journal. 2010; 16 (11): 14.
  3. Missiaen L et al. Cell Calcium. 2007; 41: 405-416.
  4. Parsons, JM. Journal of the American Academy of Dermatology. 2006; 35 (5): 653-666.
  5. Szigeti R et al. Journal of Investigative Dermatology. 2006; 126: 2370-2376.
  6. Tchernev G et al. Revista Medica de Chile. 2011; 139: 633-637.