Metastatic Crohn's Disease

ABSTRACT: Metastatic Crohn's disease is the term used for granulomatous lesions of Crohn's disease involving sites other than the gastrointestinal tract. Metastatic Crohn's disease has been considered uncommon, when in actuality it may simply be underdiagnosed or misdiagnosed since the clinical findings can be different. We report on three patients with this condition: one with generalized plaques, another with perineal and perianal ulcerations, and a third with a painless forearm nodule.

IN 1932, Crohn and colleagues described an entity characterized by granulomatous inflammation, primarily affecting the terminal ileum.1 Subsequently, it was shown that the entity could also involve the colon, and in 20% to 30% of cases the disease is limited to the colon.2,3 Crohn's disease (CD) can involve sites other than the gastrointestinal (GI) tract and is then termed metastatic Crohn's disease. Involvement of multiple body locations including skin, mucous membranes, respiratory tract, bone, and muscles have been reported.4-13 The diagnostic feature of CD is the presence of non-caseating granulomas by conventional microscopy.

The etiology of this granulomatous process is unknown. Immunoregulatory, infectious, psychosomatic, dietary, vascular, traumatic, and hormonal problems have all been implicated in the pathogenesis of this disease.1

Skin involvement occurs in up to 44% of patients with CD.6 The incidence of cutaneous lesions is much higher in patients who have colon disease as compared with those having only ileal involvement.14 The skin can be affected either contiguously, as seen in perianal, peristomal, and perifistular ulcers or distantly, in which case any part of the skin can be affected. In metastatic CD, the cutaneous lesions suggest that the same pathologic process that occurs in the GI tract is also occurring in the skin. Other cutaneous disorders that can affect patients with CD include pyoderma gangrenosum, erythema multiforme, aphthous ulcers, erythema nodosum, and necrotizing vasculitis.15 While these cutaneous disorders may be observed in patients with or without CD, metastatic CD has only been reported in patients who are ultimately diagnosed with intestinal CD. Skin lesions in some cases precede the intestinal manifestations.16 We describe three patients with metastatic CD whose lesions are similar microscopically but different clinically.

DISCUSSION

Metastatic Crohn's disease has been dubbed a great imitator, since it may mimic such entities as factitial dermatitis, intertrigo, severe acne, hidradenitis suppurativa, chronic cellulitis, erythema nodosum, severe seborrheic dermatitis, and impetigo.15 In most cases, however, a preceding history of CD affecting the GI tract and the finding of non-caseating granulomas on skin biopsy establish the correct diagnosis.17 Non-caseating granulomas are not a prominent feature in most of the diseases already mentioned. Granulomas, however, are observed in sarcoidosis and foreign body reactions, as well as mycobacterial and fungal diseases. These possibilities must be considered and ruled out by both clinical and laboratory investigation when considering the possibility of Crohn's disease.18 In patients without documented GI disease, non-caseating granulomas on skin biopsy should prompt a detailed GI history and workup. In two of our three cases, the GI and skin diagnoses were made concurrently.

The clinical presentations of our patients varied greatly. The first patient had multiple papules and plaques, with central crusts on the trunk, arms, and legs that were mildly pruritic and were diagnosed as impetigo by his private physician. Skin biopsy, however, did reveal a granulomatous dermatitis consistent with metastatic CD.

Perianal complications with CD are common, whereas perineal and genital lesions, present in our second patient, are much less frequent. Slaney et al19 reported a patient with a penile lesion that was initially thought to be syphilis. However, repeated serologic tests were negative, and histologic evaluation revealed inflammatory granulation tissue and epithelioid granulomas. In our second patient, the idea of Behçet's syndrome was considered, since urogenital lesions may be encountered with this syndrome. At the time of the initial histopathologic examination of our patient's perineal lesions, the granulomas were missed. This is not surprising, since the granulomas of CD may be poorly formed or absent in some affected areas, requiring serial sections and a high index of suspicion. One study of perianal involvement with CD revealed granulomas in 25 of 29 cases.20

Numerous therapies have been used to treat this disease, including systemic corticosteroids, sulfasalazine,15 azathioprine,17 and even metronidazole.21 Intralesional steroid injections have been met with success in some cases.22 More aggressive treatments for perineal and genital lesions, such as excision, local debridement, chemical applications, and fecal diversion have been used.23-25 Presently, there does not appear to be any one optimal or definitive treatment for metastatic CD.

Contrary to what one might expect, the correlation between cutaneous lesions of CD and GI inflammatory activity is variable. In most reports, skin and intestinal symptoms do not necessarily occur simultaneously.18 Accordingly, our third patient's GI disease was quiescent when a nodule developed on his forearm. Some studies, however, report resolution of skin lesions with resolving intestinal symptoms. This was the case with our first patient, who had dramatic improvement of both skin and GI symptoms after beginning systemic therapy. In some cases, granulomatous skin lesions may be the first indication of impending development of intestinal disease. Our second patient had severe skin involvement in the absence of any GI symptoms. In this case, cutaneous manifestations alone triggered the GI investigation, which confirmed the diagnosis of CD.

In summary, metastatic CD is an entity that may be easily misdiagnosed. The skin lesions can begin with various symptoms and may occur in the absence of intestinal symptoms. Demonstration of a granulomatous dermatitis on skin biopsy is essential, and, at times, serial histopathologic sections may be necessary. The greatest challenge exists in the patient who initially has skin lesions in the absence of GI symptoms. In such a setting, a high index of suspicion and open communication are necessary on both the part of the clinician and the pathologist.