Cutaneous manifestations of metastatic Crohn's disease

Metastatic Crohn's disease is a rare cutaneous complication of primary Crohn's disease. It is a granulomatous inflammatory process, similar to the pathogenic mechanism of Crohn's disease, that occurs in sites discontiguous from the gastrointestinal tract. Metastatic Crohn's disease can precede the development of Crohn's disease by months to years, and children are more likely to present with metastatic Crohn's disease in the absence of gastrointestinal symptoms. Given that approximately 30% of individuals with Crohn's disease present in childhood, early recognition of extraintestinal manifestations of Crohn's disease such as metastatic Crohn's disease can aid in timely diagnosis and management of bowel disease. We present data from two pediatric cases of metastatic Crohn's disease recently seen at our institution in addition to the 61 reported cases of pediatric metastatic Crohn's disease in the literature. This review article will focus on the epidemiology, pathogenesis, clinical features, and histology of and treatment options for pediatric metastatic Crohn's disease.     

METASTATIC CROHN'S DISEASE OF EXTERNAL GENITALIA

Metastatic Crohn''s disease is an uncommon extraintestinal manifestation of Crohn''s disease. Its hallmark features include the presence of cutaneous noncaseating granulomas that are noncontiguous with the gastrointestinal tract or fistula. We report a rare case of metastatic Crohn''s disease involving the external genitalia in a 14-year-old girl. Diagnosis was based on skin biopsy. Patient had complete recovery on treatment with oral and topical steroids along with azathioprine.     

Granulomatous cheilitis and Crohn''s disease

A case of granulomatous cheilitis is reported in whom investigations showed intestinal involvement compatible with Crohn's disease, although the patient had no gastrointestinal symptoms. Granulomatous cheilitis (GC) is an uncommon disorder that is characterized by persistent swelling of the lips and a granulomatous histology. Since the report of a case of GC that occurred several years before intestinal lesions appeared,¹ GC has been recognized to be an early manifestation of Crohn's disease. However, to our knowledge only four cases have been reported that initially presented with GC and then developed Crohn's disease.^1–4 Whether GC represents an early manifestation of Crohn's disease or a distinct clinico-pathological entity remains controversial.⁵ We describe a patient with GC who had intestinal lesions compatible with the diagnosis of Crohn's disease, although she had no gastrointestinal symptoms.     

Disseminated metastatic cutaneous Crohn's disease

Metastatic cutaneous Crohn's disease, in which non-caseating granulomatous infiltration of the skin occurs at sites separated from the gastrointestinal tract by normal tissue, is the least common dermatological manifestation of Crohn's disease. We report the case of an 18-year-old man who developed very widespread metastatic cutaneous Crohn's disease 2 years after he had first developed mild oral and anal lesions. His gastrointestinal symptoms had been satisfactorily controlled for 18 months with sulphasalazine alone prior to his developing skin lesions. The cutaneous lesions responded rapidly to oral prednisolone which was tailed off over 5 months and then withdrawn. He relapsed 6 months later and now requires a low dose of oral prednisolone to control the skin lesions. The only complication of this therapy has been exacerbation of mild acne vulgaris.     

Further evidence for an association between psoriasis, Crohn's disease and ulcerative colitis

To test the hypothesis that psoriasis is associated with Crohn's disease and ulcerative colitis, 204 patients with inflammatory bowel disease (116 with Crohn's disease and 88 with ulcerative colitis) and 204 age and sex matched controls were interviewed and examined. The prevalence of psoriasis in Crohn's disease (11.2%) and in ulcerative colitis (5.7%), was significantly greater than in the control group (1.5%). The prevalence of psoriasis in first degree relatives of patients with inflammatory bowel disease was also increased. It is suggested that there is a relationship between psoriasis, ankylosing spondylitis, sacroiliitis, peripheral arthropathy and inflammatory bowel disease, which may be explained by common genetic factors.     

Dermatological manifestations of crohn's disease

SUMMARY— A part from occasional case reports Crohn's disease has received little attention in the dermatological literature. Of 138 cases studied 44% were found to suffer from skin complications including abscess formation and ulceration in the peri-anal regions, groins or anterior abdominal wall. Less frequent were erythema nodosum, pyoderma gangrenosum and the skin manifestations of a malabsorption syndrome. The literature on the pathology and clinical features of Crohn's disease is briefly reviewed. The skin complications encountered are described, and their diagnostic importance is emphasized since their onset may precede any clinical manifestations of intestinal disturbance.     

Metastatic Crohn's disease in a boy presenting with genital swelling

Cutaneous manifestations of Crohn's disease are uncommon and occasionally can affect the genitals with varying symptomatology. When cutaneous features precede or occur in the absence of GI symptoms, this condition may remain undiagnosed. We report the case of a 14-year-old boy who presented for evaluation of persistent penile edema with clinicopathological features consistent with a diagnosis of genital metastatic Crohn's disease, successfully treated with infliximab.     

Vulvar swelling as the first presentation of Crohn's disease in children—A report of three cases

Vulvar swelling is a rare manifestation of metastatic Crohn's disease in children. It often predates gastrointestinal symptoms and can be the first presentation of pediatric Crohn's disease. We report three cases of pediatric Crohn's disease presenting with vulvar swelling. We discuss this rare presentation and its treatment and highlight the importance of recognizing it so that prompt investigation and appropriate management can be initiated.     

Crohn's Disease with Cutaneous Polyarteritis Nodosa in a Child: A Case Report

A 10-year-old boy presented with a 1-day history of multiple painful erythematous skin lesions on his upper and lower extremities. He was admitted to the Department of Pediatrics with persistent right lower abdominal pain and diarrhea. Punch biopsy of a skin lesion on his lower leg showed necrotizing granulomatous vasculitis with septal panniculitis consistent with polyarteritis nodosa, and our differential diagnosis included cutaneous manifestations of Croh''s disease. Abdominal ultrasonography revealed distended colonic loops suggestive of inflammatory bowel disease. Upper and lower gastrointestinal endoscopy revealed lesions involving the duodenum, cecum, colon, and rectum. He developed multiple perianal fistulas during hospitalization. Additional laboratory tests revealed positive results for anti-saccharomyces cerevisiae and antinuclear antibodies. Based on his clinical presentation and laboratory findings, he was diagnosed with Crohn''s disease associated with cutaneous polyarteritis nodosa. We report a rare case of a child who presented with cutaneous polyarteritis nodosa as an extraintestinal manifestation of Crohn''s disease.     

Azathioprine‐induced Sweet's syndrome and published work review

Hypersensitivity to azathioprine can manifest with a wide clinical spectrum. Azathioprine‐induced Sweet's syndrome (SS) is rare and usually overlooked because it can mimic disease exacerbation and sepsis. This study aims to characterize the clinical findings of azathioprine‐induced SS. A retrospective analysis of the records of three patients diagnosed with azathioprine‐induced SS and a review of the relevant English‐language published work was performed. Twelve (71%) of the 17 patients were male, ranging 9–89 years in age (mean, 47.2). The time of onset after starting azathioprine was 5–28 days (mean, 13.3). The most common associated disease was inflammatory bowel disease including ulcerative colitis and Crohn's disease (76%). The clinical features typically consisted of fever and classic rash of SS with pustules and vesicles. The lesions occurred most commonly on the face and trunk. Systemic involvement was rare and no hypotension or shock was reported as seen in azathioprine hypersensitivity syndrome. Thiopurine methyltransferase activity is not predictive of this type of adverse effect. Most patients dramatically responded to systemic corticosteroids. Azathioprine‐induced SS may be underdiagnosed because it can be easily misinterpreted as inflammatory bowel disease‐associated skin eruption. Patients with inflammatory bowel disease may be at higher risk of this condition. Early recognition and drug withdrawal can decrease morbidity of the patients.     

Melkersson-Rosenthal Syndrome with Genitalia Involved in a 12-Year-Old Boy

Melkersson–Rosenthal syndrome (MRS) is an uncommon granulomatous disease characterized by the triad of relapsing facial paralysis, orofacial swelling, and fissured tongue. Genital swelling in MRS is rarely reported. We presented the first case of complete MRS with genital swelling in a child. Biopsy examinations of both the child''s lower lip and penis showed noncaseating granuloma and intralymphatic granuloma infiltration. No symptoms or signs of other systemic disease (Crohn''s disease or sarcoidosis) were observed after 2 years of follow-up. Genetic screening for CARD15/NOD2 in this patient showed negative, which further confirmed the diagnosis of MRS. Eleven other cases of suspected complete or incomplete MRS with genitalia involved were reviewed. Our case emphasizes the specific clinical feature of MRS with genitalia involved, which was genetically different from Crohn''s disease and could be an independent entity. Lymphatic obstruction is responsible for localized edema in MRS.     

CROHN''S DISEASE OF THE MOUTH

A patient with histologically proven Crohn's disease of the ileum and caecum presented with unusual ulceration of the mouth 3 years after subtotal colectomy. Worsening of bowel symptoms was associated with exacerbation of oral ulceration on several occasions. The areas of ulceration in the mouth were in relation to a sarcoid reaction typical of Crohn's disease.     

Adolescent “Saxophone Penis” Secondary to Crohn's Disease: Misdiagnosed as Being Posttraumatic

We describe a patient with a “saxophone penis” mistakenly diagnosed as having posttraumatic changes. A careful history and attention to blood tests at presentation may have alerted clinicians that there was a nontraumatic cause for our patient's disease. It is essential that clinicians consider “metastatic” anogenital Crohn's disease as a possible cause of “saxophone penis”.     

Facial granulomatous lymphoedema and syringomyelia

The term orofacial granulomatosis was introduced for orofacial lesions which resemble Crohn's disease clinically and histologically in patients without gastrointestinal disease.¹ The Melkersson-Rosenthal syndrome and its oligosymptomatic form Meischers granulomatous cheilitis are usually felt to be part of the same spectrum of disease.² Oedema usually involves tissues of the lower half of the face.² We describe a patient with histological changes consistent with those found in orofacial granulomatosis, but with isolated localized oedema of the right periorbital tissues. The patient also had syringomyelia which has not previously been described in association with orofacial granulomatosis.     

Psoriasis,the liver,and the gastrointestinal tract

Psoriasis is a common chronic inflammatory, immune‐mediated skin disease that is frequently associated with comorbidities including psoriatic arthropathy, chronic inflammatory bowel diseases, and cardio‐metabolic disorders. In particular, nonalcoholic fatty liver disease affects about half of patients, Crohn's disease 0.5% and celiac disease 0.2–4.3% of patients with psoriasis. Some shared genetic traits as well as common inflammatory pathways may underlie these associations. The presence of comorbidities has important implications in the global approach to patients. In particular, traditional systemic antipsoriatic agents could negatively affect cardio‐metabolic comorbidities as well as nonalcoholic fatty liver disease and may have important interactions with drugs commonly used by psoriasis patients. Moreover, patients with psoriasis should be encouraged to drastically correct their modifiable cardiovascular and liver risk factors, in particular obesity, alcohol consumption, and smoking habit, because this could positively affect both psoriasis and their life expectance.     

Oral manifestations of inflammatory bowel disease: a review based on the observation of six cases

Inflammatory bowel disease (IBD) comprises two chronic, tissue‐destructive, clinical entities: Crohn's disease (CD) and ulcerative colitis (UC), both immunologically based. Bowel symptoms are predominant, but extra‐intestinal complications may occur, including involvement of the oral cavity. Oral involvement during IBD includes several types of lesions: the most common are aphthae; uncommon lesions include, among others, pyostomatitis vegetans and granulomatous lesions of CD. Starting with a presentation of six patients with oral manifestations, which were crucial for the final diagnosis of IBD, a review on the subject is presented. Oral involvement in IBD may be previous or simultaneous to the gastrointestinal symptoms. However, in the majority of cases, bowel disease precedes the onset of oral lesions by months or years. In many patients, the intestinal symptoms may be minimal and can go undetected; thus, most authors believe that the bowel must be thoroughly examined in all patients with suspected IBD even in the absence of specific symptoms. Usually, the clinical course of oral lesions is parallel to the activity of IBD; therefore, oral manifestations are a good cutaneous marker of IBD.     

Anti‐Tumor Necrosis Factor α–Related Psoriatic Lesions in Children with Inflammatory Bowel Disease: Case Report and Systematic Literature Review

We report a child with Crohn's disease and infliximab‐induced guttate psoriasis. We also performed a systematic literature review on this intriguing paradoxical phenomenon in children with inflammatory bowel disease.     

Tumor necrosis factor-α inhibitor-induced morphea and psoriasiform dermatitis in a pediatric patient with Crohn's disease

Tumor necrosis factor-alpha inhibitor therapy for inflammatory bowel disease may be associated with paradoxical cutaneous adverse events, most commonly psoriasiform eruptions. We present the case of a pediatric female patient with Crohn's disease who developed multiple concurrent cutaneous eruptions while on infliximab treatment, including morphea, psoriasiform dermatitis, and genital lichen sclerosus. Although refractory to skin-directed treatments, all three conditions resolved upon discontinuation of infliximab, supporting their development as a paradoxical reaction to infliximab therapy.     

Granulomatous cheilitis (Miescher)

A case of granulomatous cheilitis (Miescher) is reported. No aetiological factors could be determined and investigation failed to demonstrate evidence of sarcoidosis or of tuberculosis. The histology was not typical of these tatter conditions, but was consistent with that of Crohn's disease although there was no systemic evidence for this disorder. The occurrence of labial Crohn's disease preceding other manifestations has only recently been described (Carr, 1974). Careful assessment of this case and review of the literature has led us to the conclusion that granulomatous cheilitis is a distinct entity, although it can be difficult to distinguish from labial Crohn's disease.     

Visceral leishmaniasis with cutaneous symptoms in a patient treated with infliximab followed by fatal consequences

Leishmaniasis is an infectious disease caused by parasitic flagellates of the genus Leishmania. The authors present a case of 44‐year‐old man with Crohn's disease treated successfully with infliximab. This case report shows rare visceral leishmaniasis with cutaneous symptoms in an immunocompromised patient. Skin manifestations may occur before or after the visceral infection and they are often diverse.