
==== Front
JAAD Case Rep
JAAD Case Rep
JAAD Case Reports
2352-5126
Elsevier

S2352-5126(24)00295-9
10.1016/j.jdcr.2024.07.024
Case Report
A rare case of radiation-induced pemphigus foliaceus in a 70-year-old female
Ko Michelle BA myko@mednet.ucla.edu
a∗
Wu Jessica MD b
Lor Michael MD b
Hu Mengjun MD b
Holland Vanessa MD b
a David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California
b Division of Dermatology, Department of Medicine, University of California, Los Angeles, Los Angeles, California
∗ Correspondence to: Michelle Ko, BA, David Geffen School of Medicine at the University of California, Los Angeles, 855 Tiverton Dr, Los Angeles, CA 90024. myko@mednet.ucla.edu
10 8 2024
10 2024
10 8 2024
52 8084
© 2024 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.
2024
American Academy of Dermatology, Inc.
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Key words

pemphigus foliaceus
radiation
Abbreviation used

PF pemphigus foliaceus
==== Body
pmcIntroduction

Pemphigus foliaceus (PF) is an autoimmune skin condition in the pemphigus family that is caused by antibodies against desmoglein 1. Cases are limited to the skin without mucosal involvement.1 PF typically occurs in patients aged 50-60 years, with equal male-to-female distribution and higher prevalence in those with Ashkenazi Jewish descent or Mediterranean ethnic/racial backgrounds.1 The most common causes of PF have been thought to include sporadic genetic mutations, endemic etiologies (consisting of both environmental factors and susceptibility genes), and medications such as those containing thiol moieties.1 Management of PF predominately focuses on immunosuppression, with corticosteroids as the first-line treatment, and steroid sparing agents often coadministered, including rituximab, mycophenolate mofetil, and azathioprine.1 With proper treatment, clinical improvement of PF is expected to occur within weeks. Here, we report a rare case of a 70-year-old female with a history of invasive ductal carcinoma of the right breast treated with radiation, who developed PF within the field of radiation with subsequent more diffuse, albeit sporadic, involvement of the torso, which was relatively quickly controlled with oral steroids and rituximab treatment.

Case presentation

A 70-year-old female with a history of radiation for invasive ductal carcinoma of the right breast presented with a 9-month history of a pruritic rash on the breast, chest, and back (Fig 1, A and B). One year ago, the patient underwent a right breast lumpectomy with sentinel lymph node biopsy and was diagnosed with grade 2 invasive ductal carcinoma at stage 1A (pT1c, pN1a (sentinel node), cM0), using the Staging Form of the eighth Edition of the American Joint Committee on Cancer. Immunohistochemistry revealed the carcinoma to be estrogen receptor (+), progesterone receptor (+), and human epidermal growth factor receptor 2 (−), with Ki-67 positive rate 10% to 15%. After the operation, the patient was treated with 6 weeks of radiation treatment for her breast cancer, for which she was treated with a total of 1400 centigray of radiation. One month into her radiation treatment, the patient developed a pruritic rash with confluent purple plaques (Fig 1, A and B), and was treated with several courses of oral and topical antibiotics and topical steroids without improvement. One month after completing her radiation treatment, the patient was started on letrozole, an aromatase inhibitor. Other medications at the time included atorvastatin, levothyroxine, metformin, metoprolol, omeprazole, and sertraline.Fig 1 A and B, Initial presentation: Confluent purple plaques with superficial scale on the right breast and right upper chest and coin-shaped plaques on the left chest. C and D, Post-treatment: Postinflammatory hyperpigmented plaques, patches, and macules in areas of previous active lesions.

Biopsy of the rash showed psoriasiform and spongiotic dermatitis with focal eosinophilic spongiosis and prominent superficial acantholysis (Fig 2). Direct immunofluorescence revealed more than 1-2 epithelial intercellular staining with antiserum to IgG, more than 1 epithelial intercellular staining with antisera to IgG4 and C3, and negative staining with antisera to IgM (Fig 3). Paraneoplastic pemphigus panel, including indirect immunofluorescence to murine and rat substrates, was nonreactive, and a pemphigus panel, including indirect immunofluorescence to monkey esophagus (1:640) and human skin substrates (1:320), as well as ELISA desmoglein 1 (249U/mL) and desmoglein 3 (12 U/mL), showed significantly elevated autoantibodies to desmoglein 1 per ELISA (MESACUPMBL Bion). Complete blood count and comprehensive metabolic panel were within normal limits. Given the serologic findings and morphology of the rash, particularly with localization to the field of radiation, the patient was diagnosed with PF felt to be triggered by her radiation. In addition to topical clobetasol and tacrolimus ointment, she was started on a prednisone taper over 2 months and given 2 doses of rituximab 1000 mg 2 weeks apart, which resulted in improvement and eventual resolution of her rash (Fig 1, C and D).Fig 2 A-C, Psoriasiform and spongiotic dermatitis with focal eosinophilic spongiosis and prominent superficial acantholysis.

Fig 3 Direct immunofluorescence revealed greater than 1-2 epithelial intercellular staining with antiserum to IgG.

Discussion

Although there have been several case reports of radiation-induced pemphigus vulgaris, as well as other immunobullous disorders such as bullous pemphigoid, reports of radiation-induced PF are rare (Table I). The first case of radiation-induced PF was reported by Beutner et al in 1976 as part of a study of 234 patients investigating potential etiologies of different types of pemphigus, though Beutner did not provide any descriptive information or history about the patient.2 Since then, a handful of case reports have been published demonstrating this phenomenon.3, 4, 5, 6, 7Table I Literature review of cases of radiation-induced pemphigus foliaceus

Article	Age	Sex	Reason for radiation	Quantity of radiation	Time of initial presentation	Clinical presentation	Location	Treatment	Outcome	
Tagami et al 1976	41	M	Thymoma, myasthenia gravis	3000 cGy of cobalt 60	1 mo after initiating radiation treatment	“Pruritic vesicular eruption”	Irradiated site (chest at location of thymus), trunk, limbs	Oral dapsone (treatment failure), oral steroids, oral azathioprine	Improved	
Gordon et al 1990	70	F	Poorly differentiated laryngeal squamous cell carcinoma	6000 cGy of cobalt 60	1 mo after completing radiation treatment	“Persistent moist desquamation...pruritic vesicles…blisters, erythema, scaly erosions”	Irradiated site (irradiation port) to anterior chest, upper back, shoulders	Oral steroids	Resolution	
Cianchini et al 2005	70	F	Adenocarcinoma of the breast	6000 cGy	12 mo after initiating radiation treatment	“Scaly, crusted erosions on an erythematous base”	Irradiated site (left breast) to chest, upper back and arms	Oral dapsone	Resolution	
Ambay et al, 2006	92	F	Intraductal carcinoma in situ (breast cancer)	5040 cGy	3 mo after completing radiation therapy	“Sharply demarcated thin scaling erythema limited to the irradiated site and erythematous edematous plaques on trunk and extremities…with potato chip scale”	Irradiated site (L breast), trunk, andextremities	Unspecified	Unspecified	
Inadomi 2015	65	F	Unspecified breast cancer	50 Gy of electron beam therapy	2 mo after radiation treatment	“Scaly erythema...with erosions”	Irradiated site (L breast) to trunk, extremities, forehead and cheeks	Oral steroids	Resolution	
Columns with a “-” indicate that the information was unspecified in the literature.

In the few case reports of radiation-induced PF, most patients were treated for breast cancer, although one was treated for laryngeal squamous cell carcinoma4 and another for thymoma/myasthenia gravis.3 For all cases, initial blistering eruptions were confined to the areas of radiation before becoming more generalized, with latency periods ranging from a few weeks to 1 year after radiation. In addition, there has been no apparent correlation between cumulative radiation doses and the extent to pemphigus eruptions.

Other conditions included in our differential diagnosis for this patient’s symptoms included contact dermatitis, radiation dermatitis, cellulitis/erysipelas, eczematous processes, blistering processes (PF, pemphigus vulgaris, and bullous pemphigoid), and paraneoplastic processes. One important condition that was considered was carcinoma erysipeloides, particularly given this patient’s breast cancer and radiation history. Carcinoma erysipeloides represents lymphatic spread of a primary tumor, often appearing after chemotherapy, radiotherapy, or excisional surgery, and is almost exclusively associated with breast cancer.8 It typically presents as an erythematous, well-demarcated patch or plaque on the chest wall that resembles erysipelas, though it has also been reported to present as papules, ulcerations, nodules, crusting, or fungating masses. Ruling out this diagnosis requires a biopsy, which in our patient ultimately demonstrated PF, most likely associated with radiation therapy.

The majority of cases of ionizing radiation-induced PF resolved with systemic steroids, though use of azathioprine and dapsone has been reported, as well. Ionizing radiation-induced pemphigus has a similar prognosis and therapeutic approach compared to endogenous pemphigus. First-line treatment of endogenous pemphigus includes systemic corticosteroids with or without an immunosuppressive adjuvant. Intravenous anti-CD20 monoclonal antibodies, such as rituximab, have been recommended for those with new-onset moderate-to-severe pemphigus or for patients who do not achieve clinical remission with first-line therapy. Additional corticosteroid-sparing agents used for PF include azathioprine, mycophenolate mofetil, intravenous immunoglobulin, immunoadsorption, and cyclophosphamide.9

The pathophysiology of radiation-induced pemphigus is hypothesized to be due to the interference of immune surveillance from radiation-induced suppression of T-suppressor cells and disruption of the sulfhydryl groups on the pemphigus antigen, leading to an antibody reaction.10

This case demonstrates that PF can be a rare complication of radiation that warrants further recognition and awareness in treatment of oncological and dermatological conditions.

Conflicts of interest

None disclosed.

Funding sources: None.

Prior presentation: This case report was previously presented at the Pacific Dermatological Association Meeting from July 27-30, 2023 in San Francisco, California.

Patient consent: The authors obtained written consent from patients for their photographs and medical information to be published in print and online and with the understanding that this information may be publicly available. Patient consent forms were not provided to the journal but are retained by the authors.

IRB approval status: Not applicable.
==== Refs
References

1 Malik A.M. Tupchong S. Huang S. Are A. Hsu S. Motaparthi K. An updated review of pemphigus diseases Medicina (Kaunas) 57 10 2021 1080 10.3390/medicina57101080
2 Beutner E.H. Chorzelski T.P. Studies on etiologic factors in pemphigus J Cutan Pathol 3 2 1976 67 74 10.1111/j.1600-0560.1976.tb00849.x 993399
3 Tagami H. Imamura S. Noguchi S. Nishitani H. Coexistence of peculiar pemphigus, myasthenia gravis and malignant thymoma Dermatologica 152 3 1976 181 190 10.1159/000251246
4 Gordon L.T.C. Low G.J. Keeling J.H. Ionizing radiation-induced pemphigus: case presentations and literature review Arch Dermatol 126 10 1990 1319 1323 2221936
5 Cianchini G. Lembo L. Colonna L. Puddu P. Pemphigus foliaceus induced by radiotherapy and responsive to dapsone J Dermatol Treat 17 4 2006 244 246 10.1080/09546630600921197
6 Ambay A. Stratman E. Ionizing radiation-induced pemphigus foliaceus J Am Acad Dermatol 54 5 Suppl 2006 251 252 10.1016/j.jaad.2005.12.024
7 Inadomi T. A case of pemphigus foliaceus aggravated in an irradiated area by radiotherapy against breast cancer Indian J Dermatol 60 1 2015 93 94 10.4103/0019-5154.147818 25657410
8 Mekheal E. Kania B. Hawran R.A. Kumari P. Kumar V. Maroules M. Carcinoma erysipeloides: an underdiagnosed phenomenon of cutaneous metastases of breast cancer Am J Case Rep 24 2023 e937843 10.12659/AJCR.937843
9 Murrell D.F. Peña S. Joly P. Diagnosis and management of pemphigus: recommendations of an international panel of experts J Am Acad Dermatol 82 3 2020 575 585.e1 10.1016/j.jaad.2018.02.021 29438767
10 Ruocco V. Pisani M. Induced pemphigus Arch Dermatol Res 274 1 1982 123 140 10.1007/BF00510366 7165361
