Crohn disease, skin alterations K50.9

Crohn's disease is defined as: idiopathic, discontinuous and segmental, chronic inflammatory granulomatous bowel disease of unknown etiology of the entire gastrointestinal tract with preferential localization in the terminal ileum and colon. The entire gastrointestinal tract from mouth to anus may be affected. The disease may present with multiple granulomatous, often painful, ulcerated skin and oral mucosal manifestations.

Complications include stenosis, fistulae, malnutrition (see also Crohn's disease).

Incidence: 6/100.000 inhabitants/year.

Crohn's disease is probably mediated by autoimmunological processes. In addition to genetic influences (mutations in chromosome 12 and 16 are discussed - see below Crohn's disease), dietary factors, oral anticonceptives, smoking, the intestinal flora and the permeability of the intestinal wall play a role. A disturbed permeability of the mucosa seems to be etiologically significant. Mutations of the so-called NOD receptors are thought to play a pathogenetic role. First data, the disease could be triggered by bacterial antigens, seem to gain importance. Mycobacterium avium paratuberculosis (MAP) is considered the main suspect.

Further associations are known, for example with the autophagy factor ATG17L1 and the interleukin receptor IL23R.

Mostly before the age of 30 with emphasis on the 2nd and 3rd decades of life. Oral mucosal involvement occurs in 4-20% of sufferers.

No sex predilection.

In the relatively rare metastatic Crohn's (Mißnomen), women outnumber men (about 75% of the clientele). The age of manifestation here averages 34.5 years. Children are an extreme exception (20 cases in the world literature).

Abdominal pain with (usually non-bloody) mucopurulent diarrhea, meteorism, constipation, weight loss. Abdominal pain also appendicitis-like or colicky in the right lower abdomen with mild temperature elevation.

Classification of the clinic according to the Montreal classification:

• A: age of manifestation: A1<16yrs; A2 17-40yrs; A3>40yrs.
• L: Localization: L1=ileum; L2=colon; L3=ileocolonic; L4=upper GI tract.
• B: Biological behavior: B1= nonstructural/penetrating; B2= stricturing; B3 internally penetrating; B3p: perianally pentrating.

Skin/near-skin mucosal manifestations:

• Fistula formations (40%), perianally located aphthous ulcerations, anorectal abscesses (25%) - Note: often anal fistulas are the first monitoring signs of enteritis regionalis!
• Acne-like granuloma formation, also abscesses, on buttocks, lower abdomen and thighs. Occasionally also on forearms and lower legs. Face mostly free.
• Hidradenitis suppurativa
• Erythema nodosum, erythema exsudativum multiforme, vasculitis leukocytoclastic, palmar erythema, uncharacteristic pustulosis of the skin.
• Persistent genital edema
• Recurrent or permanent, usually deep, extensive, and very painful oral mucosal ulcers (4-20% of Crohn's disease cases). Frequency more common than with habituated aphthae. They are significantly larger and more painful.
• Chronic, inflammatory, cheilitis granulomatosa-like, plaque formation or swelling of the lips (see Cheilitis granulomatosa or orofacial granulomatosis; see below. Illustrations)
• Coincidence with pyoderma gangraenosum has been described
• coincidence with acrodermatitis enteropathica possible
• single coincident cases of Sweet syndrome have been described.

Eyes (7%)

• episcleritis, iritis, concunctivitis

Joints (20%)

• occurrence of arthritides and ankylosing spondylitis (80% HLA-B27 positive); sacroilitis

Liver

• Fatty liver, primary sclerosing cholangitis (K83.0)

Growth disorders in children

• Malabsorption syndrome with weight loss

Intestinal stenosis with signs of (sub)ileus, rarely perforations

Specific immunological parameters: pANCA are found in enteritis regionalis (Crohn's disease) in about 20%, in ulcerative colitis in about 65% of cases. Antibodies against yeasts, Saccharomyces cerevisiae, (ASCA) are frequently found in enteritis regionalis, less frequently in ulcerative colitis. Other antibodies are found against tropomyosin in ulcerative colitis, but not in enteritis regionalis.

Typical endoscopic findings: Disseminated mucosal lesions with often segmental involvement and frequently small bowel involvement.

Histology with epithelioid cell granulomas involving all wall layers.

Small bowel contrast examination according to Sellink with typical findings of stenosis in the terminal ileum.

Floridity can be monitored by the inflammatory parameters among the laboratory values (ESR, CRP, alpha2-globulin, fibrinogen).

Tuberculosis, sarcoidosis, ulcerative colitis; acne conglobata.

The main clinical differential diagnoses of the most common granulomatous and non-granulomatous diseases of the skin.

Therapy of skin and mucosal lesions requires parallel treatment of inflammatory bowel disease (first-line therapy: 5-aminosalicylic acid preparations + systemic glucocorticoids.

TNF-alpha blockers(infliximab and adalimumab).

AK against interleukin 10

Vedolizumab (^Entyvio®) is a, since May 2014 approved, gut-selective integrin antagonist that can be used in patients with active moderate to severe form of Crohn's disease and ulcerative colitis. Vedolizumab blocks the adhesion molecule alpha4beta7 integrin (see also under integrins).

Surgical therapy for obstruction, perforation, abscess and fistula formation.

The term "metastatic Crohn's disease" is defined as a sterile, granulomatous, cutaneous lesion without direct connection to the gastrointestinal tract. On the one hand, the term implies a malignant neoplastic process as the underlying disease, on the other hand it is misunderstood that Crohn's disease is a "non-monotopic" granulomatous systemic disease.

• Case 1:
  • 13-year-old girl with intermittent occurrence of painful, itchy genito-anal swelling and redness since LJ 4. Various unsuccessful pretreatments due to lesions falsely diagnosed as erysipelas or contact allergic eczema. Last 2-4 times/day occurrence of unformed stools with blood deposits.
  • Findings: Slightly reduced AZ, slim EZ and depressive mood. Massive, doughy swelling and reddening of the labia majora and partially of the labia minora with coarse infiltration. In the area of the rima ani with preference of the perianal region an erosive, partly coarsely infiltrated, tumorous tumor-like efflorescence with greasy coatings and inflammatory component was observed.
  • Laboratory: Accelerated SPA, moderate CRP elevation, leucocytosis at 13.000/µl, Hb 10.8 g/dl, reduced corpuscular volume, markedly decreased ferritin level, ASL titre at 1157 U/ml.
  • Colonoscopy: Floride Crohn's colitis, histology of the terminal ileum with distinct lymphofollicular hyperplasia, severe chronic inflammatory signs of epithelioid-cell granulomas in the coecum and rectum and fissure necrosis.
  • Histology of the skin: Chronic lymphedema with fibrosclerosis and abundant ectatic lymphatic vessels. In the perivascular area macrophages including some giant histiocytic cells and accumulations of epithelioid-cellular granulomas associated with vessels were found in addition to a loose lympho-plasmacellular infiltration.
  • Therapy and course: Initiation of therapy with mesalazine and metronidazole (3 times/day 200 mg p.o.); reduction of stool frequency and healing of genital findings. Continued close outpatient care. Recurrence after 2 years. Combination therapy of corticosteroids (prednisolone 50 mg/day p.o.) and metronidazole (dosage see above). Improvement of findings after 3 weeks; continuation of therapy by the pediatric clinic.
• Case 2:
  • 32-year-old female patient with painful mucosal lesions on the palate that have been present for 2 days. The patient's AZ was slightly reduced (fatigue, tiredness, loss of appetite).
  • Clinically, an oval, painful ulceration with a diameter of about 0.1 cm was found on the hard palate on the right side. In the area of the soft palate several highly inflammatory "aphthoid" areas about 0.3 cm in diameter. The gingiva, periodontium and the remaining mucosal areas were clinically o.B. A dentogenic cause of the palatal mucosal lesions could be excluded clinically and radiologically.
  • Histology of the oral mucosa: Severe acute ulcerative stomatitis with lymphocytic infiltration and few giant cells within the mucosal extravasations; no complete formation of typical epithelial cell granulomas.
  • The targeted general examination revealed a previously unknown and also currently clinically (gastro-energeologically) not active Crohn's disease. Immediate systemic therapy with prednisolone for 5 days and local analgesic irrigation with Bepanthen and subcutin solutions alternately led to complete remission within a short time.

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