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On-line version ISSN 1806-4841
An. Bras. Dermatol. vol.84 no.6 Rio de Janeiro Nov./Dec. 2009
Metastatic Crohn's disease without intestinal clinical manifestation*
Marcelo D'Ambrosio FernandesI; Helena D'Ambrosio FernandesII; Rosângela DelizaIII; Caio Eduardo Ferreira PiresIV; Angela Cristina BortoncelloVISpecialist in Dermatology, former resident, Complexo Hospitalar Padre Bento de Guarulhos Guarulhos (SP), Brazil
IISpecialist in Dermatology, former resident, Hospital das Clínicas da Universidade Estadual de Campinas (UNICAMP) Campinas (SP), Brazil
IIIPathologist, specialization course in digestive pathology taken in Japan. Specialist by the Brazilian Society of Pathology (Sociedade Brasileira de Patologia - SBP) - cidade (sigla estado), Brazil
IVResident Physician, Clinical Practice, Hospital Municipal Dr. Mário Gatti - Campinas (SP), Brazil
VResident Physician, Clinical Practice, Hospital Municipal Dr. Mário Gatti - Campinas (SP), Brazil
The authors report the case of a 47-year-old female patient with dispersed
ulcerated skin lesions that appeared 7 years before medical follow-up. Histopathological
and endoscopic findings of such lesions led to the diagnosis of a rare disorder:
metastatic Crohn's disease. This diagnosis is even more relevant because
there is no case report in the literature of Crohn's disease restricted
to cutaneous lesions, without major gastro-intestinal complaints.
The authors report the case of a 47-year-old female patient with dispersed ulcerated skin lesions that appeared 7 years before medical follow-up. Histopathological and endoscopic findings of such lesions led to the diagnosis of a rare disorder: metastatic Crohn's disease. This diagnosis is even more relevant because there is no case report in the literature of Crohn's disease restricted to cutaneous lesions, without major gastro-intestinal complaints.
Keywords: crohn disease; fistula; granuloma
Skin ulcers translate circumscribed tissue loss, normally of epidermis and dermis, which may cause impairment of the hypodermis. They may have traumatic, vascular, infectious or inflammatory etiology. In the clinical diagnostic approach of dermatological ulcerated lesions, systemic assessment of the patient is mandatory, because many times the cutaneous manifestation of the pathology results from primary non-cutaneous affection.
This is what happens in ulcers related to vasculitis, deep mycoses, mycobacteriosis and Crohn's disease, a primary entity that affects the digestive tract but that may cause cutaneous manifestations by contiguity of the intestinal affection or not 1.
In some occasions, the systemic affections are not evident through signs and symptoms, they are mild or masked, but they should not be underestimated. In Crohn's disease, there is the classical intestinal disorder together with abdominal pain in severe cases, mucosanguinolent diarrhea, weight loss and sometimes acute abdomen episodes secondary to intra-abdominal adherences 2. However, in many situations the affection does not reach clinical magnitude and digestive complaints may be less expressive. Colonoscopy, for example, in any of the possibilities, seem to be a supportive diagnostic method of great value, because even in cases of mild intestinal impairment, with almost absent clinical manifestations, there may be the confirmation of Crohn's disease diagnosis based on macroscopic and microscopic criteria.
Forty-seven year-old woman searched for medical care because of a 7-year complaint of infiltrated and ulcerated nodules and plaques, painless, recovered by a crust on the breast and right nipple, gluteus, suprapubic region, popliteal region and left ankle (Figures 1, 2 and 3). Some lesions had drainage of yellowish fluid secretion, without elimination of grains. Two of them had started after a trauma - intramuscular injection in the gluteus and suprapubic lesion caused over the c-section scar.
She did not report use of medication or previous history of diseases. She had no fever, weight loss or oral/genital ulcerations. She had no digestive or urinary findings or related family history. Upon the physical examination, there were only skin lesions. The biopsy of the ankle showed ulcerated chronic inflammatory process with marked lymphohistiocytarian reaction without signs of malignancy and BAAR and fungi analyses were negative. The tissue culture was also negative for mycobacteria and fungi.
Complete blood count, renal function test, liver profile, chest x-ray, urine analysis 1 and serum complement were all within the normal range. Serology for HIV, hepatitis B and C, FAN and ANAC were not reagent. ESR was 29 mm (1st hour) and Tuberculosis was not reactive. Serology for Leishmaniasis was negative. We ordered colonoscopy that showed erosions of terminal ileum recovered by fibrin, with clinical pathology diagnosis of moderate chronic ileitis, superficially erosive, suggesting Crohn's disease (Figures 4 and 5).
A new skin biopsy was performed, from the breast, leading to the result of ulcerated and granulomatous inflammatory process without the presence of fungi or mycobacteria and no lymphocytarian halo, compatible with Crohn's disease (Figure 6). The administered treatment was mezalasine and prednisone, without any response. The patient is currently waiting to start treatment with infliximab.
Crohn's disease is an idiopathic intestinal inflammatory disease which may affect the whole digestive tract, from the oral cavity to the anal border. It is manifested in any age range, with affected and healthy mucosa areas. However, there is evident predilection for the terminal ileum 1.
Inflammatory affections - detected by colonoscopy - in the form of mucosa erythema and edema, frequent ulcerations and formation of pseudopolyps - may lead to stenoses and loss of intestinal mobility, with disabsoprtion presentations and secondary nutritional deficits, among which, there is zinc deficiency (with clinical manifestations similar to that or enteropatic acrodermatitis), pellagra and pernicious anemia 2. It is also classically associated with nodous erythema, pyoderma gangrenosum, and cutaneous necrotizing vasculitis 3. There is a report of intestinal Crohn's disease associated with acute pustulous psoriasis 4.
It is frequent to have specific cutaneous lesions in Crohn's disease, usually contiguous to the intestinal involvement, clinically manifested as perianal fistulas and ulceration 5. In the literature, there is an entity characterized by cutaneous lesions with granulomatous aspect in the histopathology analysis without topographic correlation with intestinal Crohn, that is, specific lesions separated from intestinal affection by large areas of normal skin. It is the so-called Metastatic Crohn's disease (MCD) 7. In this case, there is predilection for genital affection - which is observed in 2/3 of the cases of MCD in children and in youngsters below the age of 18 years, and also lower limbs (38% of the cases), trunk and abdomen (24%), upper limbs (15%), face and lips (11%), and joints (8%). Generalized affection in metastatic Crohn's disease is observed in less than 4% of the cases 7. In our case, the patient had impairment of the lower limbs (ankle and knee), lower abdominal region (suprapubic region), trunk (breast) and hip (gluteus).
In the differential diagnosis with MCD we should include pyoderma gangrenosum, atypical mycobacteriosis, cutaneous tuberculosis, deep mycosis, actinomycosis, Behçet disease, Wegener granulomatosis, and cutaneous nodous polyarteritis 5. In the reported case, clinical pathology, microbiological and serology exams excluded those hypotheses and the request for colonoscopy, despite absence of abdominal pain, weight loss or diarrhea, wanted to rule out the diagnosis of MCD. Considering the macroscopic and microscopic findings of intestinal Crohn's disease, the diagnosis would be presumptive if it were not for the new skin biopsy (breast) that showed granulomatous reaction.
Kafity published an article that correlated 100% of the time the presence of intestinal disease and MCD 7. In our case, the patient presented moderate inflammatory activity of the ileum, without clinical manifestations. However, the disease activity was evident in the skin lesions.
Cutaneous Crohn's disease tends to have chronic progression and the treatment of the gastrointestinal disease leads to reduction of some skin lesions. The surgical excision of the affected portion of the digestive tract was not directly correlated with improvement in skin lesions 8.
There are many therapeutic options. Metronidazole, oral corticoids, sulfasalazine, tetracycline, azathioprine and cyclosporine are some of the options, providing favorable results, but no standardized treatment response or duration 5. The side effects of these drugs when used chronically limit their prescription. Cyclosporine seems to be useful to induce remissions and to treat acute exacerbations, when corticoids fail, but hypertension and renal failure are common in the long run 8.
If there is no clinical response with the suggested drugs, there is the option of using biological drugs - a new therapeutic class with anti-cytokine activity - which has proven to be effective 9. To control the inflammatory activity of classical Crohn's disease, the following drugs have been approved - adalimumab and infliximab. The latter has anti-TNF alpha action and has been used in a study published by Cohen in 2001 with good tolerability and control of fistulized cutaneous lesions 9,10. The action of these monoclonal antibodies has promoted quick and long lasting clinical improvement in the published series 10.
The publication by Kafty, in 1993, correlated intestinal disease with MCD in 100% of the cases. However, it did not describe pure histological intestinal involvement, without evident clinical complaints, as observed in our case. Thus, the presentation of a case with clinical inflammatory activity of Crohn's disease limited to the skin in a patient without expressive intestinal complaints deserves to be highlighted because we have to consider this entity as part of the differential diagnosis of ulcerated lesions, even if there is no digestive impairment.
1. Felley C, Mottet C, Juillerat P, Froehlich F, Burnand B, Vader JP, et al. Fistulizing Crohn's disease. Digestion. 2005;71:26-8. [ Links ]
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7. Kafity A, Pellegrini A, Fromkes J. Metastatic Crohn's disease: a rare cutaneous manifestation. J Clin Gastroenterol. 1993;17:300-3. [ Links ]
8. Saschar D. Maintenance therapy in ulcerative colitis and Crohn's disease. J Clin Gastroenterol. 1995;20:117-22. [ Links ]
9. Farrel RJ, Shah SA, Lodhavia PJ, Alsahli M, Falchuk KR, Michetti P, et al. Clinical experience with infliximab therapy in 100 patients with Crohn's disease. Am J Gastroenterol. 2000;95:3490-7. [ Links ]
10. Cohen MD. Efficacy and safety of repeated infliximab infusions for Crohn's disease: 1-year clinical experience. Inflamm Bowel Dis. 2001;(Suppl 1):S17-22. [ Links ]
Mailing Address: Funding: None * Study carried
out in a dermatology private practice in Campinas (SP), Brazil.
Marcelo D'Ambrosio Fernandes
Rua Sacramento, 501 Centro.
13010 210 Campinas SP
Tel:/Fax: 19 32363224; 19 32581127; 19 81117893
Conflict of interest: None.
* Study carried out in a dermatology private practice in Campinas (SP), Brazil.