Crohn’s disease, a well-known subtype of inflammatory bowel disease, is an inflammatory condition of the gastrointestinal tract with numerous possible extra-intestinal manifestations. Approximately 40% of all patients affected by Crohn’s disease experience at least one extra-intestinal manifestations of the disease, with the skin being the most common site of extra-intestinal involvement. Other common locations of extra-intestinal involvement include the eyes, joints, and hepatobiliary system. Interestingly, an extra-intestinal manifestation may precede the formal diagnosis of Crohn’s disease in about 25% patients.
Although the underlying etiology of Crohn’s disease remains fundamentally unknown, the largely accepted theory involves exposure to “triggers” (i.e., microbial, environmental, immunological) in a genetically susceptible person. The chronic inflammatory component of Crohn disease is likely driven by altered activation of both Th1 and Th17 immune pathways with elevated levels of interleukins 23 and 17. Polymorphisms of the NOD2/CARD15 genes may further affect the innate immune response. Interestingly, patients with an altered TRAF3IP2 gene may be predisposed to developing cutaneous involvement of their Crohn's disease. Other studies have shown altered intestinal flora (shifts in composition or decreased diversity) in patients with Crohn's disease. Precise etiology and pathogenesis are also limited to the cutaneous manifestations of Crohn’s disease, but assistance in understanding and categorizing these skin findings come from the following three well-accepted categories:
Specific lesions: lesions have histopathological findings consistent with Crohn’s disease on biopsy. This may be further subcategorized to the following:
Reactive lesions: inflammatory lesions that do not share the same histopathological findings.
Associated lesions: likely develop due to shared HLA-gene types or secondary to chronic inflammatory response.
A fourth category is suggested by some authors and encompasses the cutaneous manifestations that may be induced by the treatment of Crohn’s disease, particularly with anti-TNF therapy.
The onset of Crohn’s disease may occur at any age from childhood up to the seventh decade of life, with a majority of the cases diagnosed in young adults between 15 to 30 years of age. Interestingly, approximately 25$ to 35% of all cases of Crohn’s disease are diagnosed in patients younger than 18 years of age. Both the incidence and prevalence of Crohn’s disease have been increasing over the past few decades, particularly in well-developed countries. In the United States, approximately 246 people per 100,000 population are affected by Crohn’s disease and statistically, between 20% to 33% of those patients will experience a dermatological manifestation of their Crohn’s disease.
The clinical presentation of Crohn's disease is immensely diverse and may include any or a combination of any of the following: abdominal pain, anorexia, weight loss, diarrhea, hematochezia, melena, malnutrition, fatigue, fevers, and bowel obstruction secondary to stricture formation. The cutaneous manifestations of Crohn's disease may also aid in establishing the diagnosis of Crohn's disease as their presence may antedate the formal inflammatory bowel disease diagnosis. Although Crohn's disease is well known for its ability to affect any part of the GI tract, from the oral mucosa to the anus, most of the disease is non-contiguous and restricted to the ileum and colon.
Each of the respective categories of the cutaneous manifestations of Crohn disease and their manifestations will be discussed below:
Specific lesions: lesions with histopathological findings consistent with Crohn’s disease on biopsy.
a) Cutaneous lesions which occur due to a direct extension of bowel disease to the skin and are typically seen in the perianal and orofacial areas. Clinically, on the exam, the lesions may be ulcers, fistulae, fissures, or even abscesses and on biopsy, non-caseating granulomatous inflammation can be seen. Many do not actually consider these to truly be an "extra-intestinal" manifestation of Crohn's disease.
b) Metastatic Crohn’s disease: Rare manifestation of cutaneous Crohn's disease characterized by skin lesions with findings of Crohn’s disease on biopsy, but at sites distant and noncontiguous with the GI tract (must be separated from the GI tract by normal tissue).
Reactive lesions: Inflammatory lesions that do not share the same histopathological findings, but are believed to share a similar pathogenesis with Crohn's disease, perhaps due to impaired function of neutrophils or altered cellular immunity.
Associated lesions: likely arise due to shared HLA-gene types or secondary to a chronic inflammatory response. Interestingly, the presence and severity of the cutaneous manifestations listed below generally parallel intestinal disease activity.
Treatment-induced: A novel category of cutaneous findings that are most commonly associated with the treatment of Crohn's disease with anti-TNF biologics. The cutaneous manifestations of anti-TNF treatment do not correlate with disease activity status.
The relative absence or presence of the above cutaneous extra-intestinal manifestations may be helpful in monitoring the disease course of Crohn's disease, particularly in patients displaying oral aphthous ulcerations or erythema nodosum, as they may clue to the physician to evaluate for active intestinal disease, even in relatively asymptomatic patients.
Diagnosis of Crohn's disease is generally made via endoscopic evaluation of intestinal mucosa along with biopsy showing granulomatous changes and crypt irregularities. Additional laboratory evaluation, including blood tests, may also be utilized.
Specific lesions: lesions with histopathological findings consistent with Crohn’s disease on biopsy
Reactive lesions: inflammatory lesions that do not share the same histopathological findings, but are believed to share a similar pathogenesis with Crohn's disease.
Associated lesions: likely arise due to shared HLA-gene types or secondary to a chronic inflammatory response.
In some cases, non-granulomatous skin disorders may cause lesions, these include:
Crohn disease is extremely complex and difficult to diagnose and manage. The disorder has many extraintestinal manifestations that may sometimes precede the intestinal symptoms. The skin manifestations may present around the perianal and orofacial area. The primary caregiver, nurse practitioner, emergency department physician and internist may be the first to see patients with cutaneous Crohn. Without a biopsy, the diagnosis is not possible. Hence, a thorough history should be obtained and if abdominal symptoms are present, the patient should be referred to the gastroenterologist for management. These patients are typically managed medically but many need surgery to manage the complications. These patients often develop severe anxiety and stress about the diagnosis and hence a mental health consultation should be made early in the course of the disease. The outlook for patients with Crohn disease is guarded. Almost every patient will develop a serious complication and the overall quality of life is poor.
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