Sweet Syndrome Associated with Celiac DiseaseKelley V. Eubank, Jason Nash and Madeleine Duvic

Department of Dermatology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

Abstract Neutrophilic dermatoses are a spectrum of diseases with varying presentations and similar clinical and

histologic features. The association of neutrophilic dermatosis with celiac disease has not previously been

described. We report a 43-year-old man with a history of diverticulitis who presented with mildly pruritic,

ulcerating pustules of the dorsal hands, face, elbow, and neck, clinico-pathologically consistent with the

neutrophilic dermatosis Sweet syndrome. Remission was achieved with prednisone taper, dapsone, and a

gluten-free diet.

1. Case Report

A 43-year-old Caucasian man with a history of diverticulitis

developed recurrent ulcerations on the dorsal hands, which

were associated with fever and chills. The lesions began as spon-

taneous, tender, mildly pruritic, pink pustules, which would

then enlarge and ulcerate within a few days. He was not taking

any medications prior to the eruption. Histopathologic exami-

nation of a lesional skin biopsy from an ulcer on the left dorsal

hand showed a deep, dermal, inflammatory infiltrate sparing

the vessels, and epidermal ulceration consistent with the clinical

diagnosis of Sweet syndrome. The lesions responded to treatment

with prednisone 40mg/day, which was tapered over 4 weeks.

Over the following year, the patient had multiple outbreaks

of similar lesions on his hands, elbows, face, and neck that

responded to prednisone. His symptoms worsened as he de-

veloped fatigue, night sweats, anorexia, and diarrhea with

occasional hematochezia. Because of his 28 kg (62 lb) weight

loss and anemia, with hemoglobin of 12.0 g/dL (normal

14.0–18.0 g/dL), he was evaluated for malignancy. CT scans of

the chest, abdomen, andpelviswere normal. Laboratory investi-

gations revealed elevated carcinoembryonic antigen at 3.7mg/mL

(normal 0.0–2.5mg/mL), elevated erythrocyte sedimentation

rate at 26mm in the first hour (normal 0–9mm/h), and low

serum iron at 32 mg/dL (normal 49–181 mg/dL). Carbohydrateantigen 19-9, an immunoglobulin panel, serum vitamin B12

(cyanocobalamin), and folic acid were within normal levels.

Bone marrow biopsy showed increased morphologically

atypical mast cells in the peripheral smear and biopsy specimen.

Molecular studies demonstrated no aberrant phenotype in the

mast-cell population and no mutation in exon 17 of the KIT

gene. Serum tryptase and histamine levels were normal, so the

patient was not believed to have mastocytosis.

Colonoscopy, colorectal biopsy, and esophagogastroduodeno-

scopy were negative. Duodenal biopsy demonstrated villous

blunting and chronic inflammation consistent with celiac dis-

ease. Antibody analysis revealed elevated IgA class anti-gliadin

antibodies at 61U/mL (positive >17U/mL) and anti-tissue trans-

glutaminase antibodies at 90U/mL (positive >5U/mL). After a

gluten-free diet was initiated, his skin was clear for 3 months.

His skin lesions flared during relaxation of the gluten-

free diet, which suggested that he may have dermatitis

herpetiformis. Ulcerated pustules were present on the face

(figure 1a) and right dorsal hand (figure 1b). White blood cell

and neutrophil counts were elevated. Skin biopsy showed a

dense neutrophilic infiltrate in the reticular and papillary der-

mis with papillary dermal edema and no vasculitis (figure 2).

Special stains (Gram, Fite, and Gomori’s Methenamine-Silver)

failed to reveal an infectious etiology and tissue culture was ne-

gative. Dapsone 50mg/day and prednisone starting at 40mg/dayand subsequently tapered were prescribed. To rule out atypical

dermatitis herpetiformis, a skin biopsy fromuninvolved skinwas

examined by immunofluorescence. The lack of IgA or other

deposits argued against atypical dermatitis herpetiformis. The

patient’s symptoms were controlled with dapsone 50mg and

prednisone 10mg daily.

2. Discussion

There are currently a number of different clinical entities

characterized by neutrophilic dermal infiltrates (with or

without vasculitis). Although clinically defined, these may well

CASE REPORTSAm J Clin Dermatol 2009; 10 (5): 343-345

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ª 2009 Adis Data Information BV. All rights reserved.

represent a disease spectrum. Acute febrile neutrophilic derma-

tosis (i.e. Sweet syndrome) was originally described by Dr

Robert Douglas Sweet in 1964.[1] The major features are the

abrupt onset of typical lesions with characteristic histopatho-

logic features. Minor criteria include elevation of inflammatory

markers, presence of constitutional symptoms (fever) or infec-

tion, inflammatory or malignant disease, and rapid response to

corticosteroid therapy.[2] Upper respiratory tract infections,

hematologic malignancies, inflammatory bowel disease, and

adenocarcinoma of the gastrointestinal tract are associated

with Sweet syndrome.[3] A second entity called ‘pustular vas-

culitis of the dorsal hands,’ first described by Strutton et al.

in 1995,[4] is defined by the presence of pustular infiltrated

lesions limited to the radial aspect of the dorsal hands, and by

leukocytoclastic vasculitis. Other histologic features are papil-

lary dermal edema with neutrophilic infiltrates.[4]

Galaria et al.[5] described three cases clinically resembling

pustular vasculitis of the dorsal hands; however, these cases

lacked histology of vasculitis. Galaria proposed another entity

in which the presence of vasculitis is not a defining criterion,

called ‘neutrophilic dermatosis of the dorsal hands’ (NDDH), a

subset of Sweet syndrome.[5] She suggested that NDDH but

not Sweet syndrome had ulceration. However, vesiculobullous

(or atypical) pyoderma gangrenosum also has neutrophils with

prominent ulceration and may become hemorrhagic.[6-10]

Neutrophilic dermatoses, like pyodermagangrenosum, are known

to be associated with inflammatory bowel disease.[11-12] Neu-

trophilic dermatosis on the dorsal hands, which was previously

termed atypical Sweet syndrome or pyoderma gangrenosum-

Sweet syndrome overlap, is nowmore often called NDDH than

Sweet syndrome.[13-16] In both Sweet syndrome and NDDH,

classic criteria excluded patients with leukocytoclastic vasculi-

tis; however, criteria have since been modified. Focal vascular

injury may result from the inflammatory neutrophilic in-

filtrates. Vasculitis can be present in Sweet syndrome and

NDDH, and the timing of lesional biopsy may determine its

presence or absence.[17]

Celiac disease, also known as celiac sprue or gluten-sensitive

enteropathy, is an autoimmune disorder characterized by im-

mune response to ingested gluten in the small bowel mucosa.[18]

Patients may present with diarrhea, weight loss, abdominal

cramps, or may be asymptomatic. Serologic tests for anti-

gliadin, anti-endomysial, and anti-tissue transglutaminase anti-

bodies are the initial diagnostic tests, with confirmation by

duodenal biopsy.

This patient initially presented with fever and pustular

lesions on the dorsal hands that responded to corticosteroids.

Lesions later ulcerated (consistent with NDDH). With time, he

developed similar lesions on his face, elbows, and neck, thus no

longer fitting the definition of NDDH but still consistent with

Sweet syndrome.

Sweet syndrome associated with celiac disease has not

previously been reported. Cutaneous lesions of dermatitis

herpetiformis are frequently associated with gluten-sensitive

enteropathy.[19] Dermatitis herpetiformis usually presents with

a b

Fig. 1. Ulcerated pustules on skin: (a) face and (b) dorsal hand.

Fig. 2. Histopathology of the ulcer border, showing dense neutrophilic

infiltrate in the reticular and papillary dermis with papillary dermal edema

(hematoxylin and eosin stain; original magnification ·40).

344 Eubank et al.

ª 2009 Adis Data Information BV. All rights reserved. Am J Clin Dermatol 2009; 10 (5)

urticarial plaques with superimposed small vesicles in a sym-

metrical distribution on the scalp, posterior neck, shoulders,

extensor elbows, knees, and buttocks. Immunofluorescence

staining of uninvolved skin demonstrates granular IgA

throughout the dermal papillae.

We considered the possibility that this patient had atypical

dermatitis herpetiformis with his celiac disease. There is a recent

case of a 7-year-old boy with celiac disease who presented with

non-pruritic pustules and papules on the buttocks and extensor

surfaces. Although these lesions were clinically and histologi-

cally consistent with Sweet syndrome,[20] immunofluorescence

studies were consistent with dermatitis herpetiformis and he

achieved remission with a gluten-free diet and dapsone. Of in-

terest, our patient with Sweet syndrome also improved on a

gluten-free diet but his skin lesions were not found to contain

IgA deposits during a flare-up of skin lesions.

Multiple treatments for Sweet syndrome include cortico-

steroids, colchicine, clofazimine, danazol, dapsone, potassium

iodide, and tetracyclines. Systemic corticosteroids have signifi-

cant adverse effects and the relapse rate is high (30%). NSAIDs

represent a potential alternative. Indomethacin (indometacin),

first reported to be useful in Sweet syndrome in 1977,[21] may

lead to dramatic response and a longer period free from re-

lapse.[22] Treatment of NDDH is similar. Oral prednisolone,

dapsone, or minocycline led to resolution in six of seven pa-

tients in 1–9 weeks with 50% recurrence after up to 4 years.[23]

Lesions may also spontaneously remit.

3. Conclusion

We report a case of Sweet syndrome as a rare cutaneous

manifestation of celiac disease, and found that Sweet syndrome

also responded to a gluten-free diet, in a similar manner to

dermatitis herpetiformis. Immunofluorescence studies, routine-

ly performed in celiac patients with dermatitis herpetiformis,

may be useful in distinguishing between cutaneous lesions of

Sweet syndrome and those of dermatitis herpetiformis in rare

patients.

[See also the review article on Neutrophilic Dermatoses on

pages 301-312.]

Acknowledgments

No sources of funding were used to assist in the preparation of this case

report. The authors have no conflicts of interest that are directly relevant to

the content of this case report.

References1. Sweet RD. An acute febrile neutrophilic dermatosis. Br J Dermatol 1964; 76:

349-56

2. Su WPD, Liu HNH. Diagnostic criteria for Sweet’s syndrome. Cutis 1986; 37:

167-74

3. Bourke JF, Keohane S, Long C, et al. Sweet’s syndrome and malignancy in the

U.K. Br J Dermatol 1997; 137: 609-13

4. Strutton G, Weedon D, Robertson I. Pustular vasculitis of the hands. J Am

Acad Dermatol 1995; 32: 192-8

5. Galaria NA, Junkins-Hopskins JM, Kligman D, et al. Neutrophilic dermatosis

of the dorsal hands. J Am Acad Dermatol 2000; 43: 870-4

6. Chan HL, Lee YS, Kuo TT. Sweet’s syndrome: clinicopathologic study of

eleven cases. Int J Dermatol 1994; 33: 425-32

7. Fett DL, Gibson LE, Su WP. Sweet’s syndrome: systemic signs and symptoms

and associated disorders. Mayo Clin Proc 1995; 70: 234-40

8. Von den Driesch P. Sweet’s syndrome (acute febrile neutrophilic dermatosis).

J Am Acad Dermatol 1994; 31: 535-5

9. Callen JP. Pyoderma gangrenosum. Lancet 1998; 351: 581-5

10. Bennett ML, Jackson JM, Jorizzo JL, et al. Pyoderma gangrenosum: a com-

parison of typical and atypical forms with an emphasis on time to remission.

Medicine 2000; 79: 37-46

11. Mir-Madjlessi SH, Taylor JS, Farmer RG. Clinical course and evolution of

erythema nodosum and pyoderma gangrenosum in chronic ulcerative colitis:

a study of 42 patients. Am J Gastroenterol 1985; 80: 615-20

12. McCallum DI, Kinmont PD. Dermatological manifestations of Crohn’s dis-

ease. Br J Dermatol 1968; 80: 1-8

13. Hay CR, Messenger AG, Cotton DW, et al. Atypical bullous pyoderma gang-

renosum associated with myeloid malignancies. J Clin Pathol 1987; 40: 387-92

14. Koester G, Tarnower A, Levisohn D, et al. Bullous pyoderma gangrenosum.

J Am Acad Dermatol 1993; 29: 875-8

15. Lear JT, Atherton MT, Byrne JP. Neutrophilic dermatoses: pyoderma gang-

renosum and Sweet’s syndrome. Postgrad Med J 1997; 73: 65-8

16. Walling HW, Snipes CJ, Gerami P, et al. The relationship between neutrophilic

dermatosis of the dorsal hands and sweet syndrome: report of 9 cases and

comparison to atypical pyoderma gangrenosum. Arch Dermatol 2006 Jan;

142 (1): 57-63

17. Malone JC, Stone SP, Wills-Frank LA, et al. Vascular inflammation (vascu-

litis) in Sweet syndrome. Arch Dermatol 2002; 138: 345-9

18. Torres MI, Lopez Casado MA, Rios A. New aspects in celiac disease. World J

Gastroenterol 2007 Feb 28; 13 (8): 1156-61

19. Abenavoli L, Proietti I, Leggio L, et al. Cutaneous manifestations in celiac

disease. World J Gastroenterol 2006 Feb 14; 12 (6): 843-52

20. Woollons A, Darley CR, Bhogal BS, et al. Childhood dermatitis herpetiformis:

an unusual presentation. Clin Exp Dermatol 1999 Jul; 24 (4): 283-5

21. Hoffman GS. Treatment of Sweet’s syndrome (acute febrile neutrophilic

dermatosis) with indomethacin. J Rheumatol 1977; 4: 201-6

22. Jeanfils S, Joly P, Young P. Indomethacin treatment of 18 patients with Sweet’s

syndrome. J Am Acad Dermatol 1997; 36: 436-9

23. DiCaudo DJ, Connolly SM. Neutrophilic dermatosis (pustular vasculitis) of

the dorsal hands. Arch Dermatol 2002; 138: 361-5

Correspondence: Dr Kelley V. Eubank, Department of Dermatology, Uni-

versity of Texas MD Anderson Cancer Center, Box 434, Houston, TX 77030,

USA.

E-mail: kelleyeubank@gmail.com

Sweet Syndrome and Celiac Disease 345

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