dpc-arcive

Dermatopathology: Practical & Conceptual

July – September 2010 | Volume 16, No. 3

Clinical quiz

Böer, Almut

Question

A 36-year-old patient presented with multiple pustules on the face and trunk together with erosions on the lips and tongue (Figs. 1A-D). Lesions were painful and had developed within a few weeks.

Figs. 1A-D

Clinical appearance.

What is your diagnosis?

Two biopsies were taken, one from the skin (Figs. 2A-D) and one from the tongue (Figs. 3A-D).

Figs. 2A-D

Histopathology of a biopsy taken from the lesion pictured in Figure 1B.

Figs. 3A-D

Histopathology of a biopsy taken from the lower lip.

What is your diagnosis now?

Answer

Mucocutaneous Crohn’s disease.

Comment

Skin lesions in this patient consist of pustules of various sizes, and small ulcerations. On the oral mucosa, pustules were confluent to large suppurative zones and also accompanied with ulcerations. On histopathology, the changes in the biopsy taken from the skin are very similar to those seen in Sweet syndrome: A dense and diffuse infiltrates of neutrophils is present in the dermis. The infiltrate is joined by histiocytes and few eosinophils and extensive edema is present in the papillary dermis. Leukocytoclasia is slight. In contrast to the situation in Sweet syndrome, however, obvious deposits of fibrin are seen in more than one vessel in the superficial dermis. In the biopsy taken from the oral mucosa, the changes are similar to those seen in the skin: diffuse infiltrates of neutrophils are present together with deposits of fibrin in the walls of vessels. This biopsy, however, was taken from the border of an ulceration and it is difficult to decide whether vasculitic changes are authentic for the disease or secondary to the ulceration.

At the same time that this patient developed skin lesions, he complained about bloody diarrhea. A diagnosis of Crohn’s disease was made based on results of small bowel barium follow-through, colonoscopy with inspection of the terminal ileum, and histopathologic examination of biopsies taken during colonoscopy. A patchy distribution of inflammation was seen to involve the colon and ileum, but not the rectum. On histopathology, inflammatory infiltrates involved the entire depth of the intestinal wall. Infiltrates were dominated by neutrophils which were also present in epithelial structures. Ulceration was present, too. [1]

The lesions in the skin and oral mucosa represent extraintestinal manifestations of Crohn’s disease. Such lesions develop in up to 70% of cases after the initial diagnosis of the disease. [2] They are diverse in their clinical manifestation and include changes similar to such disparate conditions as urticaria, Sweet’s syndrome, pyoderma gangrenosum , hidradenitis suppurativa, and erythema nodosum. [2,3] Few cases of facial involvement have been reported. [4,5] Not uncommonly, cutaneous manifestations of Crohn’s disease are presenting together with lesions in the oral cavity or the perianal region. [3] The term “metastatic” Crohn’s disease has been used in the past for such manifestations of Crohn’s disease in the skin. [6-9] Strictly speaking, metastasis means “displacement” and designates spread of a disease form one organ to another one. Only later, the term metastasis became reserved to malignant neoplasms. [10]

Even though in the literature granulomas are claimed to be the histopathological hallmark of cutaneous Crohn’s disease, [2,11] infiltrates rich in eosinophils [11] or neutrophils [3] also have been reported. Infiltrates may be accompanied by signs of vasculitis in some vessels in a specimen. [3,12] In some lesions infiltrates concentrate around infundibula in the form of a suppurative infundibulitis. [3] Later in the course, infiltrates of neutrophils are joined by eosinophils, lymphocytes, and macrophages. [3]

Based on histopathologic changes alone, it is often impossible to make a definite diagnosis of Crohn’s disease. In correlation with the clinical appearance and history, however, the diagnosis is made easily. Based on the histopathologic changes shown here, it can be noted that features of Sweet syndrome in company with obvious deposits of fibrin in vessel walls in the absence of frank leukocytoclasia is a clue to mucocutaneous Crohn’s disease.

Treatment of cutaneous Crohn’s disease is often unsatisfactory. Randomized controlled trials are lacking. [2] Various chemotherapeutic agents have been used such as oral metronidazole, topical and/or oral steroids, azathioprine, cyclosporine, sulfasalazine, tetracyclines, topical or systemic tacrolimus, infliximab alone or with methotrexate, and surgical treatment with oral zinc sulphate. [2]

Summary

A patient with involvement of skin and oral mucosa of Crohn’s disease is presented as a quiz. In the literature, granulomatous infiltrates have been emphasized as being typical of the condition but in the patient presented here, infiltrates were predominated by neutrophils similar to those seen in Sweet’s syndrome. Accompanying were signs of small vessel vasculitis but frank leukocytoclasia was lacking. This pattern is emphasized as a possible clue to Crohn’s disease of the skin and oral mucosa when clinical information is sparse or lacking.

Almut Böer-Auer, M.D., is a dermatopathologist at the Dermatologikum Hamburg, Germany. This article was reviewed by Juliana Jung, M.D., and Muna Shuweiter, M.D. Contact corresponding author via email: boer@dermatologikum.de .

References

1. Crohn BB, Ginzburg L, Oppenheimer GD. Regional ileitis: a pathologic and clinical entity. J Am Med Assoc 1932;99:1323-29.

2. Palamaras I, El-Jabbour J, Pietropaolo N, Thomson P, Mann S, Robles W, Stevens HP. Metastatic Crohn’s disease: a review. J Eur Acad Dermatol Venereol. 2008;22(9):1033-43.

3. Ackerman AB, Böer A, Benin B, Gottlieb GJ. Histologic Diagnosis of Inflammatory Skin Diseases. An Algorithmic Method Based on Pattern Analysis. 3rd ed.. New York: Ardor Scribendi, Ltd., 2005.

4. Ogram AE, Sobanko JF, Nigra TP. Metastatic cutaneous Crohn disease of the face: a case report and review of the literature. Cutis. 2010;85(1):25-7.

5. Hindersin S, Mönnighoff I, Schipper J, Hoffmann TK. Metastatic Crohn’s disease: manifestation in head and neck region. Laryngorhinootologie. 2009;88(2):112-5.

6. Lebwohl M, Fleischmajer R, Janowitz H, Present D, Prioleau PG. Metastatic Crohn’s disease. J Am Acad Dermatol 1984;10:33-38.

7. McLelland J, Griffin SM. Metastatic Crohn’s disease of the umbilicus. Clin Exp Dermatol 1996;21:318-9.

8. Shum DT, Guenther L. Metastatic Crohn’s disease. Case report and review of the literature. Arch Dermatol 1990;126:645-48.

9. Yosipovitch G, Hodak E, Feinmesser M, David M. Acute Crohn’s colitis with lobular panniculitis – metastatic Crohn’s? J Eur Acad Dermatol Venereol 2000;14(5):405-6.

10. http://en.wikipedia.org/wiki/Metastasis

11. Emanuel PO, Phelps RG. Metastatic Crohn’s disease: a histopathologic study of 12 cases. J Cutan Pathol 2008;35(5):457-61.

12. Sabat M, Leulmo J, Saez A. Cutaneous granulomatous vasculitis in metastatic Crohn’s disease. J Eur Acad Dermatol Venereol 2005;19(5):652-3.