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 Table of Contents  
CASE REPORT
Year : 2020  |  Volume : 4  |  Issue : 1  |  Page : 42-45

Lip swelling and constipation: Pretest probability of cutaneous signs for crohn's disease in the absence of typical gastrointestinal symptoms


1 Department of Dermatology, Keck Medical Center, University of Southern California, Los Angeles, CA, USA
2 Department of Dermatology, Keck Medical Center, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA, USA

Date of Submission23-Jul-2019
Date of Decision08-Oct-2019
Date of Acceptance01-Dec-2019
Date of Web Publication06-Jan-2020

Correspondence Address:
Minnelly Luu
Department of Dermatology, Keck Medical Center, Children's Hospital Los Angeles, University of Southern California, 4650 Sunset Blvd, Los Angeles, CA 90027
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CDR.CDR_25_18

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  Abstract 


We describe a female child in the first decade patient admitted to a children's hospital for lip swelling and constipation who was ultimately diagnosed with Crohn's disease. Her lip swelling resolved after the initial immunosuppression for her Crohn's disease. In this article, we discuss the pretest probability of cutaneous findings associated with inflammatory bowel disease in predicting a diagnosis of Crohn's disease in the absence of intestinal symptoms. Cutaneous findings including linear immunoglobulin A bullous dermatosis, pyoderma gangrenosum, lichen spinulosus, and epidermolysis bullosa acquisita are discussed.

Keywords: Crohn's disease, lip swelling, orofacial granulomatosis


How to cite this article:
Chow ML, Luu M. Lip swelling and constipation: Pretest probability of cutaneous signs for crohn's disease in the absence of typical gastrointestinal symptoms. Clin Dermatol Rev 2020;4:42-5

How to cite this URL:
Chow ML, Luu M. Lip swelling and constipation: Pretest probability of cutaneous signs for crohn's disease in the absence of typical gastrointestinal symptoms. Clin Dermatol Rev [serial online] 2020 [cited 2020 Jan 23];4:42-5. Available from: http://www.cdriadvlkn.org/text.asp?2020/4/1/42/275241




  Introduction Top


Many cutaneous manifestations have been associated with Crohn's disease.[1] The prevalence of cutaneous manifestations ranges from 21% to 40%. Extraintestinal manifestations in Crohn's are more common than that in ulcerative colitis (UC). Patients with cutaneous manifestations usually have a younger age at diagnosis of inflammatory bowel disease (IBD) compared with patients who do not have cutaneous manifestations.” We report a case of a young patient with lip swelling who was ultimately diagnosed with Crohn's disease. Her case highlighted the importance of understanding the strength of the association between cutaneous findings and Crohn's disease.


  Case Report Top


A female child in the first decade of life with a history of chronic constipation and abdominal pain was admitted to our Children's Hospital for the evaluation of unintentional weight loss and intermittent lip swelling for 2 years. By the mother's report, the patient had waxing and waning lip swelling every 2 weeks. The swelling was associated with a rash around the lips [Figure 1]. Her lips had never returned to baseline since her symptoms started. There were no associated respiratory or gastrointestinal symptoms, and no eye swelling had been observed with her lip swelling. She had been treated with diphenhydramine, topical and systemic antibiotics, and oral steroids in the past with no improvement. She had lost approximately 5 pounds over the last 2 weeks due to difficulty eating with lip swelling.
Figure 1: Lip swelling in a young patient ultimately diagnosed with Crohn's disease

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The primary team and the allergy and immunology service initiated the workup for hereditary angioedema and Melkersson–Rosenthal syndrome. Dermatology was consulted to evaluate for other causes of lip swelling. On examination, the patient was noted to have significant swelling of the upper and lower lip with perioral scaling and poorly demarcated erythematous patches. An anal fissure and two perianal pedunculated papules were present. No neurologic deficits or changes on the tongue were noted. At the time of examination, differential diagnosis was broad, including hereditary angioedema, orofacial granulomatosis, cheilitis glandularis, plasma cell cheilitis, contact dermatitis, sarcoidosis, and foreign body reaction. She was scheduled for an outpatient lip biopsy. Laboratory workup revealed mild anemia, but normal C4, C1 inhibitor, angiotensin-converting enzyme, and thyroid studies.

Fecal calprotectin was elevated. Magnetic resonance enterography revealed a perianal fistula. She underwent upper endoscopy and colonoscopy, with biopsy results revealing nonnecrotizing granulomas, focal histiocytic aggregates, increased lymphoplasmacytic infiltrates in the lamina propria of the rectum, terminal ilium, and transverse and descending colon. These changes were consistent with Crohn's disease. The gastroenterology service started the patient on prednisone and infliximab with improvement of her symptoms and lip swelling.

Many cutaneous manifestations have been associated with Crohn's disease.[1] The prevalence of cutaneous manifestations ranges from 21% to 40%. Extraintestinal manifestations in Crohn's are more common than that in ulcerative colitis (UC). Patients with cutaneous manifestations usually have a younger age at diagnosis of inflammatory bowel disease (IBD) compared with patients who do not have cutaneous manifestations.


  Discussion Top


The cutaneous manifestations of IBD are divided into several categories, including cutaneous granulomatous disease (i.e., cutaneous Crohn's), reactive diseases (e.g., erythema nodosum), nutritional deficiency secondary to bowel disease, and sequela of therapy (e.g., psoriasis). These manifestations have been divided into specific and nonspecific cutaneous manifestations. The more specific cutaneous manifestations with the same histologic features of the underlying disease include oral ulcerations, perianal and peristomal fissures, fistula, ulcers, and metastatic granulomatous cutaneous lesions. Nonspecific cutaneous manifestations of Crohn's disease include aphthous stomatitis, erythema nodosum, pyoderma gangrenosum (PG), Sweet's syndrome, bowel-associated dermatosis-arthritis syndrome, pyostomatitis vegetans, psoriasis, vitiligo, secondary amyloidosis, leukocytoclastic vasculitis, acquired epidermolysis bullosa, alopecia areata, systemic lupus erythematosus, acrodermatitis enteropathica, and angular cheilitis.[2]

Classic teaching does not prioritize these cutaneous manifestations in the frequency with which they are associated with IBD. Prioritization is important as these cutaneous signs and symptoms may be the initial presenting signs of bowel disease. In some cases, bowel symptoms may not be prominent and in our case, an atypical presentation of IBD. Thus, the goal of this discussion is to investigate the pretest probability for cutaneous features of Crohn's disease in patients with no intestinal symptoms based on a review of the literature. Symptoms are ranked based on the current literature as being likely, less likely, or unlikely associated with a diagnosis of Crohn's disease in the absence of intestinal symptoms. Prospective longitudinal studies are lacking, and thus, our conclusions are limited by the lack of information.

Epidermolysis bullosa acquisita

The prevalence of epidermolysis bullosa acquisita (EBA) in the general population is unknown. However, it is thought that 30% of patients with EBA have Crohn's disease.[3] In one review,[4] 42 cases of coincidental EBA with Crohn's disease or UC were described. In total, 35 of the 42 cases were diagnosed with Crohn's disease, and only 7 were diagnosed with UC. In 5/35 of patients, EBA preceded gastrointestinal symptoms. However, in the majority of cases, gastrointestinal symptoms preceded the onset of EBA.[3] It is thought that chronic intestinal inflammation exposes the immune system to Type VII collagen, which leads to antibodies against this type of collagen, which in turn eventually leads to EBA. Thus, in the absence of intestinal symptoms, the pretest probability of a diagnosis of Crohn's disease in a patient with EBA is unlikely.

Pyoderma gangrenosum

PG has an annual incidence of up to 10/million/year.[5] In total, 25%–50% cases of PG are thought to be idiopathic. Within the population of patients with PG, 20%–30% of patients have IBD. However, in patients with IBD, only 1%–2% of patients have PGs.[6] Interestingly, in a cohort of 2402 patients with IBD, PGs were significantly associated with erythema nodosum, which is another cutaneous finding that is thought to be associated with IBDs. Usually, PGs are diagnosed in patients with established IBD; however, some cases have been reported to precede Crohn's diagnosis. The incidence of PG in Crohn's disease and UC is approximately the same, though classic teaching is that PGs are more commonly seen in UC. Thus, in the absence of intestinal symptoms, the pretest probability of a diagnosis of Crohn's disease in a patient with PG is less likely.

Lichen spinulosus

Lichen spinulosus is a rare cutaneous condition with average age of onset characterized by hyperkeratotic papules in a follicular distribution. In the IBD literature, there are two case reports of patients with Crohn's disease and lichen spinulosus.[7],[8] One case was of a 28-year-old female with Crohn's disease found to have lichen spinulosus on the trunk, neck, and upper extremities. The other was a patient with lichen spinulosus of the groin, and he also had a history of Crohn's disease. Because there are so few cases in the literature, the pretest probability of a diagnosis of Crohn's disease in a patient with lichen spinulosus is very unlikely.

Cutaneous or metastatic Crohn's disease

There are fewer than 100 cases in the literature of cutaneous or metastatic Crohn's disease.[9] In children, <20 cases have been reported. In total, 20% of cases with cutaneous Crohn's disease had skin lesions before a diagnosis of Crohn's disease by 3 months to 8 years. However, histopathology in these patients with tuberculoid granulomas may be indistinguishable from lupus vulgaris, zirconium or beryllium granulomas, foreign body granulomas, and other infectious granulomas. A high index of suspicion must be maintained, and patients must be monitored in the absence of intestinal symptoms. The pretest probability of a diagnosis of Crohn's disease in a patient with tuberculoid granulomas, with other etiologies ruled out, should be less likely.

Linear immunoglobulin A bullous dermatosis

The incidence of linear immunoglobulin A bullous dermatosis (LAD) is 0.5–2.3 cases per million individuals per year.[10] There are approximately seven case reports in the literature linking IBD to LAD. However, within these case reports, the link to UC is more common than to Crohn's disease. In one study,[11] UC affected 7.1% of 70 adult patients with LAD. In this series, as well as case reports, all cases developed IBD before the LAD. In the referenced study, none of these patients were noted to have Crohn's disease. As a sidenote, this disease has also been associated with infliximab treatment that is sometimes used to treat IBD.[12] Thus, the pretest probability of Crohn's disease in a patient with LAD in the absence of gastrointestinal symptoms is very unlikely.

Orofacial granulomatosis

Lip swelling as observed in our case has an extensive differential diagnosis. When lip swelling does not improve with conservative measures, a histologic diagnosis is needed. We return to our original question of how high our pretest probability should have been for Crohn's disease in the absence of gastrointestinal symptoms. Our patient's lip swelling resolved after her initial infusion of infliximab, and her presumptive diagnosis was orofacial granulomatosis, though we were not able to achieve a histologic diagnosis.

The incidence of orofacial granulomatosis in the general population is unknown. There are several case series that show a strong association between orofacial granulomatosis and Crohn's disease. In one series, 37% of patients with orofacial granulomatosis without intestinal symptoms had demonstrable IBD on biopsy of the gastrointestinal tract.[13] It is known that orofacial granulomatosis may precede the gastrointestinal symptoms by several years. In one systematic review, 26% of patients had gastrointestinal symptoms at the time of diagnosis and 40% of patients at presentation received a concomitant diagnosis of Crohn's disease. Interestingly, 51.4% of patients were later diagnosed with Crohn's disease.[14] In fact, some authors suggested that orofacial granulomatosis is a subset of Crohn's disease, given the strong association. Therefore, our pretest probability even in the absence of intestinal symptoms is likely.


  Conclusion Top


Although many cutaneous findings have been associated with IBD, some findings are more specific than others. For example, orofacial granulomatosis is likely to be one of the best cutaneous findings that can predict Crohn's disease in a patient without gastrointestinal symptoms. In contrast, findings such as lichen spinulosus, EBA, and LAD are less specific findings for a diagnosis of Crohn's disease in the absence of gastrointestinal symptoms.

Declaration of patient consent

The informed consent was obtained for participation in the study and publication of data and images for research and educational purposes.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Ampuero J, Rojas-Feria M, Castro-Fernández M, Cano C, Romero-Gómez M. Predictive factors for erythema nodosum and pyoderma gangrenosum in inflammatory bowel disease. J Gastroenterol Hepatol 2014;29:291-5.  Back to cited text no. 1
    
2.
Lebwohl M, Lebwohl O. Cutaneous manifestations of inflammatory bowel disease. Inflamm Bowel Dis 1998;4:142-8.  Back to cited text no. 2
    
3.
Chen M, O'Toole EA, Sanghavi J, Mahmud N, Kelleher D, Weir D, et al. The epidermolysis bullosa acquisita antigen (type VII collagen) is present in human colon and patients with Crohn's disease have autoantibodies to type VII collagen. J Invest Dermatol 2002;118:1059-64.  Back to cited text no. 3
    
4.
Reddy H, Shipman AR, Wojnarowska F. Epidermolysis bullosa acquisita and inflammatory bowel disease: A review of the literature. Clin Exp Dermatol 2013;38:225-9.  Back to cited text no. 4
    
5.
Ruocco E, Sangiuliano S, Gravina AG, Miranda A, Nicoletti G. Pyoderma gangrenosum: An updated review. J Eur Acad Dermatol Venereol 2009;23:1008-17.  Back to cited text no. 5
    
6.
von den Driesch P. Pyoderma gangrenosum: A report of 44 cases with follow-up. Br J Dermatol 1997;137:1000-5.  Back to cited text no. 6
    
7.
Kano Y, Orihara M, Yagita A, Shiohara T. Lichen spinulosus in a patient with Crohn's disease. Int J Dermatol 1995;34:670-1.  Back to cited text no. 7
    
8.
Aloi FG, Molinero A, Pippione M. Parakeratotic horns in a patient with Crohn's disease. Clin Exp Dermatol 1989;14:79-81.  Back to cited text no. 8
    
9.
Kurtzman DJ, Jones T, Lian F, Peng LS. Metastatic Crohn's disease: A review and approach to therapy. J Am Acad Dermatol 2014;71:804-13.  Back to cited text no. 9
    
10.
Fortuna G, Marinkovich MP. Linear immunoglobulin A bullous dermatosis. Clin Dermatol 2012;30:38-50.  Back to cited text no. 10
    
11.
Paige DG, Leonard JN, Wojnarowska F, Fry L. Linear IgA disease and ulcerative colitis. Br J Dermatol 1997;136:779-82.  Back to cited text no. 11
    
12.
Hoffmann J, Hadaschik E, Enk A, Stremmel W, Gauss A. Linear IgA bullous dermatosis secondary to infliximab therapy in a patient with ulcerative colitis. Dermatology 2015;231:112-5.  Back to cited text no. 12
    
13.
O'Neill ID, Scully C. Biologics in oral medicine: Oral Crohn's disease and orofacial granulomatosis. Oral Dis 2012;18:633-8.  Back to cited text no. 13
    
14.
Lazzerini M, Martelossi S, Cont G, Bersanini C, Ventura G, Fontana M, et al. Orofacial granulomatosis in children: Think about Crohn's disease. Dig Liver Dis 2015;47:338-41.  Back to cited text no. 14
    


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