Hailey-Hailey Disease masquerading as Recurrent "Tinea cruris"

Dr Henry Foong
Ipoh, Malaysia

The patient, in his 50s, presented with a 10-year history of  recurrent pruritic skin eruptions on the groins and axilla. He was treated by his GPs as well as a urologist for "infected tinea cruris" with oral antifungals, IV antibiotics, topical steroids, topical antifungals but the treatments did not help. For the past 3 months, the lesions have worsened. He had no fever or other constitutional symptoms.  He had no history of diabetes. His father apparently had similar skin lesions. 

Examination showed erythematous plaques with vesiculation and superficial fissures and erosions on the groins extending to the scrotum, inner thighs and intergluteal cleft. The lesions appeared to be bilateral, symmetrical, hyperpigmented and well demarcated. Similar lesions were noted on the axilla. There were no bulla or purpura. There was no oral or nail lesions. KOH exam for hyphae was negative on 3 occasions.

Initial provisional diagnosis was that of tinea incognito but KOH exam was repeatedly negative.  Hailey-Hailey disease a.k.a. familial benign chronic pemphigus was considered in the differential diagnosis.  

A skin biopsy with DIF was done.  H&E shows focal and central lesion of suprabasal and intraepithelial clefts containing basophilic cells with large nuclei and a paranuclear halo.  There is a presence of basal keratinocytes attached to basement membrane forming a characteristic tombstone, or ‘‘dilapidated brick wall’’ appearance. Corps ronda cells are not prominent. The stratum corneum shows parakeratosis and hyperkeratosis with focal neutrophilic infiltrates.  The upper dermis shows perivascular infiltrate of lymphocytes, histiocytes and eosinophils.

Immunofluorescence studies show IgG, IgA , IgM, C3 were negative.

Interpretation: Acantholytic epithelial lesion consistent with familial benign pemphigus.

The management of this patient may be challenging.  General measures such as wearing lightweight and loose clothing would be helpful.  Avoiding friction on the affected areas, use of mild antiseptic solutions  and reduction in sweating are also advisable. In terms of specific treatment, we plan to start with topical calcineurin inhibitors and oral antibiotics such as doxycycline 100mg bd. Other possible options include low dose naltrexone, methotrexate, dapsone, azathioprine, etanercept, apremilast, botox and laser treatment.  Low dose naltrexone appeared to be very effective in some of the cases but may have variable responses according to the dose.

References

1. Imene Ben Lagha, Kurt Ashack, Amor Khachemoune.  Hailey Disease: An Update Review with a Focus on Treatment Data.American Journal of Clinical Dermatology Oct 2019.  https://doi.org/10.1007/s40257-019-00477-z

2. Hohl D. Darier disease and Hailey–Hailey disease. In: Bolognia J, Jorizzo J, Schaffer J, editors. Philadelphia: Elsevier Inc; 2012. p. 887–97.

3. Severine Cao, Evelyn Lilly, Steven T. Chen. Variable Response to Naltrexone in Patients With Hailey-Hailey Disease. JAMA Dermatol. 2018 Mar; 154(3): 362–363. 

68 year-old woman with subcutaneous lesions

Presented by Dr. A.R. Pito, Retired, Volunteer Dermatologist
Queens Memorial Medical Center
New York, New York

This 68-year-old woman presented for evaluation of painful lesions under the skin that have been present for 3-4 months. She has a history of psoriasis, which is in remission, fibromyalgia, hypertension.  There is no personal history of malignancy.  No exotic travel.  She had smoked over two ppd for decades.

EXAMINATION: The examination shows a woman who appears slightly older than her stated age. She has 6-8 freely movable subcutaneous smooth-surfaced lesions on the back, posterior nuchal area, and the upper chest. The largest is ~ 5 mm in diameter. The remainder of the exam plus breast palpation was unremarkable.  No adenopathy appreciated.

INITIAL MPRESSION: Subcutaneous skin lesions, present for only a short period of time. Etiology is unclear.

PLAN: An excisional biopsy was taken today from the lesion on the right upper back.

Pathology: 

The first two are H&E of nodule in the fat, showing atypical cells with duct-like vacuoles. The second two are representative immunoperoxidase stains. GATA 3 is the nuclear one (dot-like pattern) and mammoglobin is the cytoplasmic staining.
These darkly beautiful photomicrographs were taken by Dr. Lynne Goldberg at the Boston University School of Medicine's Department of Dermatopathology.

Plan:  Mammography and breast ultrasound. Referral to oncologist.
Mammography shows masses in r. breast.  Ultrasound guided biopsy planned and specimen will be sent for Estrogen receptor, progesterone receptor and Her-2 (human epidermal growth factor receptor).

Note:  In this age of "Social Distancing" it is unlikely that this disgnosis would have been make expeditiously in a woman with no history of an underlying malignancy.  We will add more as her case progresses.

Your thoughts will be appreciated.

References:

1. Mammaglobin, a Valuable Diagnostic Marker for Metastatic Breast Carcinoma Zhiqiang Wang1, et. al. Int J Clin Exp Pathol (2009) 2, 384-389

Free Full Text.

Abstract:  Identification  of  metastasis  and  occult  micrometastases  of  breast  cancer  demands  sensitive  and  specific  diagnostic  markers.  In  this  study,  we  assessed  the  utility  of  a  mouse  monoclonal  antibody  to  human  mammaglobin  for  one  such  purpose.  Immunohistochemical  stains  were  performed  on  paraffin-embedded  sections  from  a  total  of  284  cases,  which  consisted  of  primary  breast  invasive  carcinomas  (41  cases)  with  matched metastases to ipsilateral axillary lymph nodes, metastatic breast carcinoma to liver (1 case) and kidney (1 case), non-breast neoplasms (161 cases), and normal human tissues (39 cases). The results showed 31 of the 41 cases of primary breast cancer with axillary lymph node metastases were positive for mammaglobin (76%). In the meantime, we documented expression of mammaglobin in occasional cases of endometrial carcinoma (17%). Our data further validated that mammaglobin is a valuable diagnostic marker for metastatic carcinoma of breast origin, although endometrial carcinoma should be considered as a major differential diagnosis. 

2. GATA3 Expression in Common Gynecologic Carcinomas: A Potential Pitfall. Tatjana Terzic  et. al.  Int J Gynecol Pathol, 38, 485-492 2019

Abstract: GATA binding protein 3 (GATA3) immunohistochemistry is primarily used as a marker of breast and urothelial differentiation, particularly in metastatic settings. In the gynecologic tract it also serves a robust marker for mesonephric and trophoblastic tumors. Full Abstract: pubmed.gov PMID: 30059453