Hailey-Hailey Disease and Pemphigus Foliaceus; Preview: Practice PATH MD; Call for Case Reports

First Reported Case of Patient with Hailey-Hailey Disease (HHD) Developing Pemphigus Foliaceus

By Christa Super, BS, Garrett Nelson, MD, FAAD, and Sandra Marchese Johnson MD, FAAD

Hailey-Hailey Disease (HDD) is a rare autosomal dominant skin condition discovered in 1939 by the Hailey brothers.¹ It is usually observed in the third or fourth decade of life but has been reported at any age. Recent evidence shows HHD is due to a malfunctioning calcium pump.² Protein SPCA1 regulates this process. Disruption of the level of calcium in the intracellular matrix leads to compromised desmosomes. Patients can suffer painful erosive and crusted skin due to suprabasilar acantholysis of the epidermis.³

Pemphigus foliaceus (PF) is a rare autoimmune disease that has a blistering effect on the skin. The patient’s immune system mistakenly produces antibodies that attack the desmosomes of the cell which then separates keratinocytes. Fluid then fills the separated void and creates a blister. This disease can be induced by drugs or increased exposure to sunlight.³

Case Report

A 61-year-old-female presented to the dermatology clinic in April 2016. She was diagnosed with HHD at the age of 59. The patient also has a strong positive family history of the disease. The condition affects her son and mother. It is reported that most of her family members were diagnosed with HHD in the third decade of life. The patient consulted with numerous dermatologists before her visit to the clinic, but had found minimal relief. Her prior treatments included various oral and topical antibacterial agents, antiviral agents, antifungal agents, and steroidal agents.

A skin biopsy performed at the clinic demonstrated acantholytic dermatosis consistent with pemphigus foliaceus. Acantholytic dermatosis is known for causing a truncal rash consisting of crusted patches (Fig 1, Fig 2, Fig 3 and Fig 4). Direct immunofluorescence revealed intercellular IgG and C3 deposition (Fig 6). Indirect immunofluorescence (IIF) results showed 1:160 titers of IgG antiepithelial cell surface antibodies on monkey esophagus and normal results for other substrates.

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The decision was made to treat the patient with systemic prednisone and azathioprine. Prednisone use would be gradually reduced. Within one week, the patient’s condition improved significantly (Fig 5). The patient still continues to improve.

Discussion

After much debate, it was decided that the patient initially suffered from HHD and then later developed pemphigus foliaceus. Her case was of much interest because she is the first patient documented in the literature to have both conditions. It is possible that the patient’s HHD caused a reaction in her body that resulted in epitope unveiling, otherwise known as “epitope spreading.” This occurrence is caused by tissue damage due to a primary inflammatory process. From this primary response, the release and exposure of a previously “sequestered” antigen occurs, leading to a secondary autoimmune response against the newly released antigen.⁵ HHD would have been the patient’s primary response to have caused the cascade, which possibly led her to develop an autoimmune response. Pemphigus foliaceus contains autoantibodies that bind to a protein called desmoglein-1. This protein is found in desmosomes in the keratinocytes near the upper layer of the epidermis. Normally IgA or IgG autoantibodies are the most commonly found antibodies in PF, which then leads to the disruption of the keratinocytes.⁶

By gaining information about HHD and PF, physicians can better develop multidimensional treatment plans and better educate patients, especially patients who may be currently suffering from both HHD and PF simultaneously.

Sandra Marchese Johnson MD, FAAD, and Garrett Nelson, MD, FAAD, are board-certified dermatologists at Johnson Dermatology in Fort Smith, AR. Christa Super, BS is s an undergraduate student at the University of Arkansas-Fort Smith.

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3.Imbernón-Moya, Adrián et al. Pemphigus foliaceus associated with Hypericum perforatum. AAD Case Reports, Volume 2 , Issue 4 , 326 – 328.

4.Hochwalt, P. C., Christensen, K. N., Cantwell, S. R., Hocker, T. L., Otley, C. C., Brewer, J. D., & ... Baum, C. L. (2015). Carbon dioxide laser treatment for Hailey-Hailey disease: a retrospective chart review with patient-reported outcomes. International Journal Of Dermatology, 54(11), 1309-1314. doi:10.1111/ijd.12991

5.Chan Ls, et al. Epitope spreading: lessons from autoimmune skin diseases. J Invest Dermatol. 1998 Feb;110(2):103-9.

6. Lamb, Steven. “Benign Familial Pemphigus.” DermNet New Zealeand. N.p., 2001. Web. 3 Nov. 2016.