Almost half of Crohn disease (CD) patients experience a dermatologic manifestation of the disease. A rare entity, metastatic CD (MCD) presents a diagnostic challenge without a high index of suspicion. Its etiology is not well defined; however, it appears to be an autoimmune response to gut antigens. Herein, we review the etiology/epidemiology, diagnostic criteria, and treatment for this uncommon condition.
Epidemiology and Clinical Characteristics of MCD
Metastatic CD was first described by Parks et al1 in 1965 and refers to a diverse collection of macroscopic dermatologic manifestations in tissue not contiguous with the gastrointestinal (GI) tract. To be classified as MCD, the tissue must demonstrate characteristic histopathologic findings, which invariably include noncaseating granulomas.
Crohn disease may affect any part of the GI tract from the mouth to anus, with a multitude of associated cutaneous manifestations having been described. The terminal ileum is the most commonly affected portion of the GI tract in CD, but the large intestine also may be involved in 55% to 80% of cases.2 The incidence of non-MCD-associated anal lesions seems to correlate with intestinal involvement in that as few as 25% of patients with ileal-localized CD have anal lesions compared to nearly 80% of patients with large intestinal involvement.3
It has been estimated that 18% to 44% of patients with CD have some form of cutaneous manifestation,4 with MCD being a rare subcategory. As few as 100 cases have been described from 1965 to the present.5 The presence of MCD does not correlate well with severity of intestinal CD, and although a majority of MCD cases present after at least 6 months of GI symptoms,6 there are instances in which MCD presents without prior or existing evidence of intestinal CD.7
With regard to MCD, the term metastatic is sometimes supplanted in the literature by cutaneous to avoid any implication of cancer; however, due to a myriad of dermatologic manifestations, both terms can cause confusion. The categorization of the various types of cutaneous findings in CD is well summarized in a review by Palamaras et al8 with the following classifications: (1) granulomatous by direct extension (oral or perianal), (2) MCD lesions (genital and nongenital), (3) immune-related lesions, and (4) lesions from nutritional deficiencies. Of the cutaneous manifestations relating to CD, MCD is the least common cutaneous categorical manifestation and is further divided into subcategories of genital and nongenital lesions.8
The nongenital distribution of MCD is the more common variety in adults and particularly seems to affect the legs and plantar surfaces (38%), the trunk and abdomen (24%), and the face (15%).5,9 These nongenital MCD manifestations are most commonly described as nodules, ulcerations, or erythematous to purple plaques, and less commonly described as abscesses, pustules, or papules.
The sequence of cutaneous symptoms of MCD relative to intestinal disease depends to some degree on patient age. In adults diagnosed with MCD, it has been noted that a GI flare is expected 2 months to 4 years after diagnosis; however, in children the subsequent GI flare has been noted to vary more widely from 9 months to 14 years following presentation of MCD.8 Furthermore, roughly 50% of children diagnosed with MCD present concomitantly with their first symptoms of a GI flare, whereas 70% of adults with MCD had been previously diagnosed with intestinal CD.8 In one review of 80 reported cases of MCD, 20% (16/80) had no symptoms of intestinal disease at the time of MCD diagnosis, and the majority of the asymptomatic cases were in children; interestingly, the majority of these same children were diagnosed with CD months to years later.9
Both the location and characteristics of cutaneous findings in MCD correlate with age.9 Metastatic CD has been identified in all age groups; however, lymphedema is more common in children/young adults, while nodules, ulceration, and fistulating disease are more often seen in adults.10 Affected children and adolescents with MCD range from 5 to 17 years of age, with a mean age at disease onset of 11.1 years and equal incidence in males and females.8 Adults with MCD range from 18 to 78 years of age, with a mean age at presentation of 38.4 years.8,11
Concerning anatomic location of disease, adults with MCD most commonly have nodules with or without plaques on the arms and legs and less commonly in the genital area.8 In contrast, children with MCD are more prone to genital lesions, with up to 85% of cases including some degree of genital erythematous or nonerythematous swelling with or without induration.8 Genitourinary complications of CD as a broad category, however, are estimated to occur in only 5% to 20% of intestinal CD cases in both children and adults.12
There have been conflicting reports regarding gender predilection in MCD. Based on a review by Samitz et al13 of 200 cases of CD over an 18-year period, 22% of patients with CD were found to have cutaneous manifestations--presumably not MCD but rather perianal, perineal, vulvar fistulae, fissures, or abscesses--with a male to female preponderance of almost 2 to 1. A more recent review of the literature by Palamaras et al8 in 2008 reported that contiguous non-MCD affects adult females and children more often than adult males, with 63% adult cases being female. This review seems to be more congruent with other reports in the literature implicating that females are twice as commonly affected by MCD than males.9,14