CASE REPORT

pISSN 1598-9100 • eISSN 2288-1956

https://doi.org/10.5217/ir.2018.16.1.147
Intest Res 2018;16(1):147-150

A case of pemphigus vulgaris associated with ulcerative

colitis
Joo Wan Seo1, Jongha Park1, Jin Lee1, Mi Young Kim1, Hyun Ju Choi1, Heui Jeong Jeong1, Ji Woon Lee1,
So Young Jung2, Woo Kyeong Kim3
1
Division of Gastroenterology, Department of Internal Medicine, Departments of 2Dermatology, and 3Pathology, Inje University Haeundae Paik
Hospital, Inje University College of Medicine, Busan, Korea

Pemphigus vulgaris is an autoimmune bullous disorder characterized by the production of autoantibodies against the intercel-
lular space of the epithelium. It has rarely been reported in association with inflammatory bowel disease. Ulcerative colitis is
one of the forms of inflammatory bowel disease. A 62-year-old woman who had been treated for ulcerative colitis for 16 years
developed pruritic bullae on the skin of her face and body. Histological findings and direct immunofluorescence examination
of the skin showed pemphigus vulgaris. She was treated with systemic steroids, mesalazine, and azathioprine. Her cutaneous
lesions have remained in remission and her ulcerative colitis has remained well-controlled. The relationship between pemphi-
gus vulgaris and ulcerative colitis is unclear. An autoimmune response has been suspected in the pathogenesis of ulcerative
colitis. Pemphigus vulgaris is also associated with an autoimmune mechanism. To our knowledge, this is the first case of ulcer-
ative colitis associated with pemphigus vulgaris reported in Korea. The association may be causal. (Intest Res 2018;16:147-150)

Key Words: Colitis, ulcerative; Pemphigus; Autoimmunity

INTRODUCTION CASE REPORT

Pemphigus is a rare, autoimmune, blistering disorder of A 62-year-old woman presented with a 1-month history
the skin and mucosa. Pemphigus vulgaris (PV) is the most of erythematous bullae on the face, body, and both legs (Fig.
common form of pemphigus and presents as flaccid bullae 1A). She was diagnosed with UC in 1997 and prescribed
of the mucous membranes and skin, caused by acantholysis. sulfasalazine (2 g/day). The skin lesions were accompanied
Mucous membranes are initially affected, and skin lesions by itching. Crusts formed after scratching (Fig. 1B). When
develop after mucosal involvement.1 she visited the dermatology department of Inje University
UC is one form of IBD. It is estimated that 5.2% of patients Haeundae Paik Hospital, a skin biopsy was performed. His-
with UC have mucous membrane lesions and 11% have cu- topathologic findings included the formation of clefts and
taneous lesions.2 Associations with psoriasis and lichen pla- vesicles containing neutrophils and eosinophils overlying
nus have also been reported.3 However, the association of PV basal cells (Fig. 2). Biopsy for direct immunofluorescence
and UC is rare. We describe a case of PV associated with UC. was obtained from the epidermis immediately adjacent to a
blister. IgG and C3 deposition was identified in the intercel-
lular spaces, compatible with PV. After the biopsy, she was
Received October 17, 2016. Revised December 5, 2016.
Accepted January 2, 2017. Published online May 26, 2017 treated with intravenous steroids (dexamethasone 5 mg/
Correspondence to Jongha Park, Division of Gastroenterology, Department day). She developed bloody stools during administration
of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University
College of Medicine, 875 Haeun-daero, Haeundae-gu, Busan 48108, Korea. and underwent colonoscopy to determine the current status
Tel: +82-51-797-0200, Fax: +82-51-797-0298, E-mail: neakker@gmail.com of UC. Colonoscopy revealed dirty exudate, mucosal ery-

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Joo Wan Seo, et al. • A case of pemphigus vulgaris associated with UC

Fig. 1. Cutaneous features of the patient.

(A) Crust formation on nose was appeared
after scratching. (B) Pruritic erythematous
bullae filled with serous exudate showed
A B on the skin of lower leg.

DISCUSSION

We present the case of a patient who had UC associated

with PV. PV has an incidence rate between 0.1 and 0.5 per
100,000 individuals per year. The average age at onset is 40
to 60.4 PV is mediated by circulating pathogenic IgG anti-
bodies directed against the keratinocyte cell surface mol-
ecules desmoglein 3 and desmoglein 1.1 Initial symptoms
are painful erosions of the oral mucosa. Skin lesions develop
after mucosal involvement and are characterized by flac-
cid blisters and cutaneous erosions.5 Associations between
PV and other autoimmune disorders such as rheumatoid
arthritis, myasthenia gravis, lupus erythematous, and perni-
cious anemia have been reported.6 PV is not known to be a
Fig. 2. Pathologic finding of the erythematous bullae of lower leg. skin manifestation of UC. Involvement of the gastrointestinal
Microscopic findings showed a suprabasilar cleft and vesicle (white tract with PV is uncommon. There have been several reports
arrow) with 1 to 2 layers of suprabasal keratinocytes attached to base-
of esophageal involvement with PV. However, there have
ment membrane forming part of floor of the cleft. Dermal papillae were
prominent with acantholytic basal cells (black arrow) (H&E, ×400). been few reports on the association between PV and UC.7-10
In previously reported cases, 3 of 4 patients had resolu-
tion of PV after systemic steroid treatment. The other patient
thema, edema, and friability of the entire colon. Moreover, was treated with systemic steroid plus methotrexate, and
discrete ulcers in the descending and sigmoid colon were PV resolved (Table 1). In our case, the skin lesions showed
noted, consistent with severe and extensive UC (Fig. 3A). improvement after treatment with steroid and azathioprine.
Sulfasalazine was discontinued. Mesalazine (6 g/day) and In the literature, systemic steroids are the mainstay of PV
azathioprine (25 mg/day) were started. Her skin lesions treatment. Azathioprine is used as an adjuvant to systemic
and bloody stool improved, and she was discharged after steroid treatment.11 Unfortunately, in patients with pemphi-
3 weeks. For the next 14 months, she had frequent flares of gus, the risk of steroid-induced diabetes and hyperglycemia
erythematous bullae and erosions on the scalp and face that have been reported. Our patient was diagnosed with steroid-
required treatment with intravenous steroids. induced diabetes during the second admission, and has
Two years later, she underwent follow-up colonoscopy. been treated with insulin, metformin, and sitagliptin.
Healing ulcers in the distal transverse colon and descending The most common reactive skin manifestations of IBD are
colon were observed, consistent with mild UC (Fig. 3B). Aza- erythema nodosum and pyoderma gangrenosum.12 Unlike
thioprine was maintained for 19 months and then stopped these, PV is characterized by flaccid blisters and IgG antibod-
due to elevated liver enzyme levels. Steroid dose was tapered ies against keratinocyte cell surface desmosomal molecules.
and stopped after 28 months because of the improvement in In contrast, perivascular deposition of immunoglobulins
cutaneous lesions. Her UC continued to be stable. and complement are seen on direct immunofluorescence in
erythema nodosum, suggesting that the pathogenesis of ery-
thema nodosum in IBD involves an immunological reaction

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 https://doi.org/10.5217/ir.2018.16.1.147 • Intest Res 2018;16(1):147-150

Fig. 3. Colonoscopic findings. (A) Colonos-

copy showed diffuse erythema, edematous
mucosa with multiple ulceration in descend-
ing colon. (B) Follow-up colonoscopy showed
A B focal erythema and loss of vascularity.

Table 1. Clinical Features of 4 Cases of PV Associated with UC

Age Presenting feature Treatment for
Author (year) Intraoral lesions Skin lesions
(yr) of UC PV
Prendiville et al. (1994)7 11 Ulcers on gingivobuccal sulcus, No Bloody diarrhea Prednisone
tongue ulcer
Delfino et al. (1986)8 40 Erosions on oral mucosa Bullous lesions on the whole body Bloody diarrhea Prednisone,
methotrexate
Fabbri et al. (1986)9 39 Erosions on oral mucosa Bullous lesions on the back Bloody diarrhea Triamcinolone
Kacar et al. (2002)10 41 Erosion on oral mucosa No Rectal bleeding Prednisolone
PV, pemphigus vulgaris.

against common antigens in the bowel and skin. The patho- disease after proctocolectomy.16 This suggests that inflamed
genesis of pyoderma gangrenosum in IBD is also considered bowel in UC is a source of antigenic stimulation, causing im-
to be an abnormal immunological response, with cross- munobullous skin disease.
reacting autoantibodies to bowel and skin.13 Moreover, there is some speculation that the association
However, the pathogenic relationship between PV and between UC and immune-mediated mucocutaneous blis-
UC is unclear. An autoimmune mechanism is involved in tering disorders may be triggered by an epitope spreading
the pathogenesis of PV. UC is also thought to represent an mechanism.17,18 A study conducted in the United Kingdom
autoimmune response. A review of the literature suggests revealed that patients with linear IgA bullous dermatosis had
that antigens secreted by the inflamed colon cross-react a higher prevalence rate of UC.19 Uchiyama et al.20 reported
with skin antigens, resulting in pemphigus. Sotiriou et al.14 a case of IgA/IgG pemphigus combined with UC. They sug-
suggested that inflammation of the gastrointestinal mucosa gested that IgA autoantibodies might be induced by colonic
in IBD could be stimulating an immune reaction to colonic inflammation. Epitope spreading may explain the associa-
antigens, followed by cross-reactivity with antibodies to skin tion between UC and PV. In our case, UC appeared first, fol-
antigens. Nico et al.15 suggested that exposure of colonic lowed by PV, supporting the concept that inflammation of
mucosal antigens to the immune system has the potential to the colon is the inciting factor.
stimulate anti-epithelial autoimmunity, resulting in pemphi- This is the first case of UC associated with PV reported in
gus. Some reports suggested that colectomy plays a thera- Korea. This case highlights the possible causal association
peutic role in patients with UC associated with immunobul- between UC and PV. PV may be an extraintestinal dermato-
lous skin disease. Sotiriou et al.14 reported that skin disease logic manifestation of UC.
resolved in a patient who had linear IgA bullous dermatosis
and UC, while another patient who had not undergone FINANCIAL SUPPORT
colectomy needed to continue treatment due to active skin
disease. Three additional cases showed resolution of skin The authors received no financial support for the research,

www.irjournal.org 149
Joo Wan Seo, et al. • A case of pemphigus vulgaris associated with UC

authorship, and/or publication of this article. 9. Fabbri P, Emmi L, Vignoli L, et al. Chronic pemphigus vulgaris
associated with ulcerative rectocolitis: apropos of a clinical
CONFLICT OF INTEREST case. G Ital Dermatol Venereol 1986;121:355-359.
10. Kacar S, Sezgin O, Sahin T. Pemphigus vulgaris and ulcerative
No potential conflict of interest relevant to this article was colitis. Am J Gastroenterol 2002;97:507-508.
reported. 11. Chams-Davatchi C, Esmaili N, Daneshpazhooh M, et al. Ran-
domized controlled open-label trial of four treatment regimens
AUTHOR CONTRIBUTION for pemphigus vulgaris. J Am Acad Dermatol 2007;57:622-628.
12. Levine JS, Burakoff R. Extraintestinal manifestations of inflam-
J.W.S. wrote the initial draft which was then extensively matory bowel disease. Gastroenterol Hepatol (N Y) 2011;7:235-
edited by J.P. All authors were involved in critical revision of 241.
the manuscript and have approved the final manuscript for 13. Huang BL, Chandra S, Shih DQ. Skin manifestations of inflam-
submission. matory bowel disease. Front Physiol 2012;3:13.
14. Sotiriou MC, Foo CW, Scholes CT, Zone JJ. Immunobullous
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