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Cutaneous Crohn Disease

Editor: Karthik Krishnamurthy Updated: 1/9/2023 6:56:56 PM


Crohn 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 disease experience at least one extra-intestinal manifestation 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 disease in about 25% of patients.[1][2][3][4]


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Although the underlying etiology of Crohn 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 disease.[5] Other studies have shown altered intestinal flora (shifts in composition or decreased diversity) in patients with Crohn disease. Precise etiology and pathogenesis are also limited to the cutaneous manifestations of Crohn 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 disease on biopsy. This may be further subcategorized to the following:

  • Cutaneous lesion occurring due to a direct extension of bowel disease to the skin
  • Metastatic Crohn disease: skin lesions with characteristic findings of Crohn disease on biopsy, but at sites distant from the gastrointestinal (GI) tract (noncontiguous).

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 a 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 disease, particularly with anti-TNF therapy.


The onset of Crohn disease may occur at any age from childhood up to the seventh decade of life, with most cases diagnosed in young adults between 15 to 30 years of age. Interestingly, approximately 25$ to 35% of all Crohn disease cases are diagnosed in patients younger than 18 years of age. The incidence and prevalence of Crohn 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 disease, and statistically, between 20% to 33% of those patients will experience a dermatological manifestation of their Crohn disease.[2]

History and Physical

The clinical presentation of Crohn 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 disease may also aid in establishing the diagnosis of Crohn disease as their presence may antedate the formal inflammatory bowel disease diagnosis. Although Crohn 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 disease on biopsy.

a) Cutaneous lesions that 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 disease.

  • Perianal fissures/fistulae: Very common finding in up to 33% of patients with Crohn disease and is generally more indicative of colonic involvement. Some authors do not consider this to be a true extra-intestinal manifestation of Crohn disease due to its close location to the anus. Patients may develop acrochordons or "sentinel tags" in the perianal area as well.

b) Metastatic Crohn disease: Rare manifestation of cutaneous Crohn disease characterized by skin lesions with findings of Crohn disease on biopsy, but at sites distant and noncontiguous with the GI tract (must be separated from the GI tract by normal tissue).

  • Generally, the lesions are plaques and/or nodules with a red to a purple hue that may even have an ulcerative component. They may also appear similar to those mentioned above in the category of direct extension of intestinal disease. The most common sites of involvement include the intertriginous area, extremities, face, and genitalia.

Reactive lesions: Inflammatory lesions that do not share the same histopathological findings but are believed to share similar pathogenesis with Crohn disease, perhaps due to impaired function of neutrophils or altered cellular immunity.

  • Pyoderma gangrenosum (PG): Although pyoderma gangrenosum is more commonly associated with ulcerative colitis, it may still be seen in patients with Crohn disease as well. The presence of a pyoderma gangrenosum should prompt physicians to consider a diagnosis of IBD in these patients as well, as 20% to 50% of patients with PG have coexistent IBD. These lesions classically start as tender papulopustules with a surrounding erythematous to the violaceous rim. The area then starts to undergo necrosis, leading to an ulcerated area. Fully developed lesions are best described as an ulcer with a sterile, purulent base with an irregular, undermined, gun-metal border. The most common location in adults is in the lower extremities, but in children, they are more likely to occur on the head or in the anogenital region. Lesions of PG may be initiated or aggravated by seemingly minor trauma and may also exhibit pathergy. Lesions tend to heal with significant scarring. Diagnosis is generally made clinically as histopathological findings are non-specific.
  • Sweet syndrome: Sweet syndrome, also known as acute febrile neutrophilic dermatosis, is a relatively uncommon disease entity. Although it does have an association with IBD, it is more commonly seen in association with upper respiratory infections due to Streptococcus, gastrointestinal Yersiniosis infections, hematological malignancies (AML), and solid tumors of the breast, colon, and GU tract. Female patients are more commonly affected than males, and children are rarely affected. The lesions typically start as tender, erythematous, edematous papules and plaques that favor the head, neck, and upper extremities. As with pyoderma gangrenosum, the lesions of Sweet's syndrome may also exhibit pathergy. Systemic findings, including fever, leukocytosis, arthralgias, myalgias, and ocular involvement (conjunctivitis, episcleritis), are commonly seen in Sweet's syndrome. Diagnosis is generally made clinically, and biopsy generally shows a nodular and perivascular neutrophilic infiltrate.

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.

  • Erythema nodosum (EN): Erythema nodosum is a fairly common cutaneous finding associated with Crohn disease, with reports ranging from 6% to 15% of patients affected. The presence of EN is not exclusive to Crohn disease and has many other disease associations, including malignancies, pregnancy, use of oral contraceptive medications, autoimmune disease, and infections, such as streptococcus and tuberculosis. The typical clinical presentation includes a female patient with tender, erythematous nodules overlying the anterior tibia. A biopsy is seldom needed to make the diagnosis, but early lesions may reveal septal panniculitis if examined histologically. A biopsy may also prove beneficial to help rule out metastatic Crohn disease.
  • Oral lesions: Oral lesions are also a common cutaneous finding associated with Crohn disease, with approximately 10% of patients experiencing either aphthous ulcerations, pyostomatitis vegetans, or periodontitis. The presentation of each of the previously mentioned manifestations differs, but all three are similar because they cause oral pain and discomfort. Patients with aphthous stomatitis develop painful, shallow ulcerations, with a fibrinous base and surrounding erythema on the buccal or labial mucosa. Pyostomatitis vegetans also affects the labial and buccal mucosa with friable mucosa scattered with erosions and ulcerations. Peridontitis is not specific to Crohn disease or ulcerative colitis, but the more severe disease has been noted in patients with inflammatory bowel disease. The biopsy is rarely required to diagnose any of those above.

Treatment-induced: A novel category of cutaneous findings that are most commonly associated with the treatment of Crohn disease with anti-TNF biologics. The cutaneous manifestations of anti-TNF treatment do not correlate with disease activity status.

  • Anti-TNF-associated skin lesions: Anti-TNF-associated skin lesions were previously regarded as a rare occurrence but are becoming more prevalent with the popular use of anti-TNFs in numerous different disease entities, including rheumatoid arthritis and psoriasis. It has been estimated that 5% to 10% of patients with IBD treated with an anti-TNF will develop an anti-TNF induced skin lesion. Eczematous and psoriasiform skin changes are the most common findings.

The relative absence or presence of the above cutaneous extra-intestinal manifestations may help monitor the disease course of Crohn 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 disease is generally made via endoscopic evaluation of intestinal mucosa and biopsy, showing granulomatous changes and crypt irregularities. Additional laboratory evaluation, including blood tests, may also be utilized.

Treatment / Management

Treatment for the plethora of cutaneous manifestations of Crohn disease is extensively varied. Each of the manifestations that were discussed above will be briefly discussed below.[6][7][8][9][10](A1)

Specific lesions: lesions with histopathological findings consistent with Crohn disease on biopsy

  • The cutaneous lesion occurs due to a direct extension of bowel disease to the skin. In general, surgical intervention is required.
  • Metastatic Crohn disease: Treatment of metastatic Crohn disease often proves to be significantly difficult. Few therapeutic options are available with very limited information regarding the efficacy of the therapies. Case reports have suggested the use of immunomodulators, such as anti-TNF biologics or topical or systemic corticosteroids.

Reactive lesions: inflammatory lesions that do not share the same histopathological findings but are believed to share similar pathogenesis with Crohn disease.

  • Pyoderma gangrenosum (PG): Goals of treatment should include reduction of the inflammatory process to promote healing, pain reduction, and control of underlying IBD (particularly if PG lesions seem to parallel Crohn disease course). Patients should be educated about daily wound care, and referral to a wound care center may be helpful. Generally, the first-line systemic therapy for PG is systemic corticosteroids (0.5 to 2 mg/kg/day), and concurrent use of local corticosteroid therapy may be implemented as well. Should the PG prove refractory to corticosteroids, oral or intravenous (IV), cyclosporine, or anti-TNF agents should be considered. Surgery and debridement should be avoided as a treatment for PG due to potential pathergy. Unfortunately, remission may be short-lived because as many as 25% of patients will experience recurrent disease.
  • Sweet's syndrome: Disease is self-limited, and most lesions completely resolve without scarring in 1 to 3 months, but recurrence occurs in about one-third of patients. Oral corticosteroids such as prednisone (0.5 to 1 mg/kg/day) may be used for 4 to 6 weeks, and lesions generally improve or resolve quickly. For localized disease, topical or intralesional steroids may be more appropriate.

Associated lesions: likely arise due to shared HLA-gene types or secondary to a chronic inflammatory response.

  • Erythema nodosum: Disease is self-limited and resolves without scarring. As the presence of erythema nodosum tends to parallel the activity of intestinal disease, treatment directed at achieving better control of the patient's Crohn disease is recommended. Leg elevation, compression hose, and pain control should be implemented as well. In severe or refractory cases, systemic corticosteroids (0.5 to 1 mg/kg/day) should be initiated. Anti-TNF agents may be required if there is an absence of an adequate response to prednisone.
  • Oral lesions: Oral lesions such as aphthous ulcerations, pyostomatitis vegetans, and periodontitis disease activity are positively correlated to underlying intestinal disease activity. First-line management should aim to achieve better control of Crohn disease with supportive care with antiseptic and analgesic mouthwashes plus or minus local corticosteroids.

Treatment-induced: A novel category of cutaneous findings most commonly associated with Crohn disease treatment using anti-TNF biologics.[11][12][13](B3)

  • Anti-TNF-associated skin lesions: As previously stated, withdrawal of the anti-TNF should resolve the lesions; however, this is often not necessary as the eczematous or psoriasiform skin changes may be managed with various topical treatments, including topical corticosteroids, emollients, vitamin D analogs, and phototherapy.

Differential Diagnosis

In some cases, non-granulomatous skin disorders may cause lesions; these include:

  • Pyoderma gangrenosum
  • Neutrophilic dermatosis or Sweet syndrome
  • Pyodermatitis-pyostomatitis vegetans with snail-track ulcers
  • Erythema multiforme
  • Erythema nodosum
  • Acneform eruptions with nodulocystic acne, hidradenitis suppurativa, and folliculitis
  • Palisaded neutrophilic and granulomatous dermatitis
  • Necrotizing and granulomatous small vessel vasculitis


The prognosis for these cutaneous manifestations closely conforms to the prognosis for Crohn disease. In instances of treatment-induced cutaneous Crohn disease, withdrawal of the anti-TNF medications should effect a resolution.


The complications of cutaneous manifestations of Chron disease are similar to the complications for those cutaneous conditions when they do not accompany Crohn disease.

Deterrence and Patient Education

Since treatment for Crohn disease is palliative as opposed to curative, the patient will need to remain vigilant to any changes in their condition and remain compliant with all their medications. This needs to be a focus of all follow-up visits.

Enhancing Healthcare Team Outcomes

Crohn disease is extremely complex and difficult to diagnose and manage, and such it requires an interprofessional team including primary care clinicians, specialists (gastroenterologists and dermatologists), NPs and PAs, nurses, and pharmacists. All these disciplines need to coordinate their activities and communicate openly to work as a unit to improve patient outcomes. [Level 5]

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 disease. 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.[14][15][16]



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