Ulcerative colitis and rashes

Contents

Crohn skin disease

What is Crohn disease?

Crohn disease is an inflammatory bowel disease that involves inflammation of the small intestine. This can cause pain, fever, constipation, diarrhoea and weight loss. Extraintestinal features are common in Crohn disease and include arthritis, skin problems, inflammation in the eyes or mouth, gallstones and kidney stones. Crohn disease affects about 1 in 300 Europeans and has peak onset in the teens and 20s.

When granulomatous lesions of Crohn disease involve sites other than the gastrointestinal tract, the disease is termed metastatic Crohn disease.

What are the clinical features of cutaneous Crohn disease?

Skin involvement or cutaneous Crohn disease occurs in about 40% of patients with Crohn disease.

Extension of intestinal Crohn disease

Skin tags, swelling (oedema), fissures and abscesses around the perineal and perianal region are common in patients with Crohn disease. Painful vulval or scrotal fissures and ulceration may occur. See DermNet NZ’s page on genital Crohn disease.

Metastatic Crohn disease

Metastatic granulomatous cutaneous Crohn disease may present as spots or plaques found on the trunk, arms and legs. Lesions tend to be asymmetrical and involve dermis and or subcutaneous tissue (panniculitis). They may be mildly itchy.

Cutaneous reactions to intestinal Crohn disease

In some cases, non-granulomatous skin disorders occur as a reaction to the intestinal disease. These include:

  • Pyoderma gangrenosum
  • Neutrophilic dermatosis / Sweet syndrome, typically with pustules
  • Pyodermatitis-pyostomatitis vegetans, a purulent erosive dermatosis characterised by snail-track ulcers
  • Erythema multiforme
  • Erythema nodosum
  • Acneform eruptions including nodulocystic acne, hidradenitis suppurativa and folliculitis
  • Palisaded neutrophilic and granulomatous dermatitis
  • Necrotizing and granulomatous small vessel vasculitis.

Occasionally, skin lesions may occur before any signs or symptoms of the intestinal disease.

Oral Crohn disease

Oral involvement occurs in 8-9% of Crohn disease and may include:

  • Gingival or mucosal swelling
  • Cobblestoning of the buccal mucosa
  • Aphthous ulcers
  • Mucosal tags
  • Angular cheilitis
  • Granulomatous cheilitis (persistent lip swelling).
Skin complications of Crohn disease

Secondary skin eruptions

Crohn disease affecting the gut may lead to malnutrition. Iron deficiency and vitamin deficiencies may present as skin or oral ulceration, persistent infections or pellagra.

Drugs prescribed for Crohn disease may also lead to adverse effects on the skin (drug eruptions).

How is Crohn skin disease diagnosed?

Skin biopsy of the lesion is performed. The histopathological finding of non-caseating granulomas similar to those found in intestinal Crohn disease supports the diagnosis of Crohn skin disease. In patients with no intestinal disease whose skin biopsy shows non-caseating granulomas, a thorough gastrointestinal history and systemic work-up should be performed.

The presence of anti-Saccharomyces cerevesiae (ASCA) antibodies in the blood are very suggestive of Crohn disease, with 60% sensitivity and 90% specificity.

* Granuloma on skin pathology

What is the treatment of Crohn skin disease?

Treatment for Crohn skin disease is palliative not curative.

Treatment of the intestinal manifestations usually improves the skin lesions. Treatment may include:

  • Oral corticosteroids
  • Intralesional steroids injected into or around skin lesions
  • Antibiotics such as metronidazole and tetracycline, usually prescribed for weeks to months
  • Methotrexate
  • Azathioprine
  • Sulfasalazine
  • Anti-tumour necrosis factor (TNF) agents such as infliximab and adalimumab.

Acne treatment and inflammatory bowel disease: What is the evidence?

To the Editor: The association between inflammatory bowel disease (IBD) and acne treatment has gained much attention from the media and has led to legal concerns. We aim to inform dermatologists of studies examining the link between IBD and isotretinoin, and IBD and tetracyclines, as such studies have primarily been published in the gastroenterology literature. PubMed queries (“isotretinoin,” “antibiotic,” “tetracycline,” “minocycline,” or “doxycycline” followed by “inflammatory bowel disease,” “Crohn disease,” or “ulcerative colitis”) yielded 10 pertinent studies.

An association between isotretinoin and IBD was first discussed in the mid-1980s1x1Schleicher, S.M. Oral isotretinoin and inflammatory bowel disease. J Am Acad Dermatol. 1985; 13: 834–835
Abstract | Full Text PDF | PubMed | Scopus (33) | Google ScholarSee all References, 2x2Brodin, M.B. Inflammatory bowel disease and isotretinoin. J Am Acad Dermatol. 1986; 14: 843
Abstract | Full Text PDF | PubMed | Scopus (30) | Google ScholarSee all References; several cases have since been described.3x3Crockett, S.D., Gulati, A., Sandler, R.S., and Kappelman, M.D. A causal association between isotretinoin and inflammatory bowel disease has yet to be established. Am J Gastroenterol. 2009; 104: 2387–2393
Crossref | PubMed | Scopus (43) | Google ScholarSee all References IBD patients who did not experience worsening of their condition using isotretinoin have also been reported.4x4Rosen, T. and Unkefer, R.P. Treatment of pyoderma faciale with isotretinoin in a patient with ulcerative colitis. Cutis. 1999; 64: 107–109
PubMed | Google ScholarSee all References Two case-controlled studies have recently been published (Table ITable I).5x5Bernstein, C.N., Nugent, Z., Longobardi, T., and Blanchard, J.F. Isotretinoin is not associated with inflammatory bowel disease: a population-based case-control study. Am J Gastroenterol. 2009; 104: 2774–2778
Crossref | PubMed | Scopus (84) | Google ScholarSee all References, 6x6Crockett, S.D., Porter, C.Q., Martin, C.F., Sandler, R.S., and Kappelman, M.D. Isotretinoin use and the risk of inflammatory bowel disease: a case-control study. Am J Gastroenterol. 2010; 105: 1986–1993
Crossref | PubMed | Scopus (103) | Google ScholarSee all References Bernstein et al5x5Bernstein, C.N., Nugent, Z., Longobardi, T., and Blanchard, J.F. Isotretinoin is not associated with inflammatory bowel disease: a population-based case-control study. Am J Gastroenterol. 2009; 104: 2774–2778
Crossref | PubMed | Scopus (84) | Google ScholarSee all References did not demonstrate an association between IBD and isotretinoin, whereas Crockett et al6x6Crockett, S.D., Porter, C.Q., Martin, C.F., Sandler, R.S., and Kappelman, M.D. Isotretinoin use and the risk of inflammatory bowel disease: a case-control study. Am J Gastroenterol. 2010; 105: 1986–1993
Crossref | PubMed | Scopus (103) | Google ScholarSee all References demonstrated an association between ulcerative colitis and isotretinoin. The database in the study of Crockett et al included more IBD cases, but Bernstein et al’s study database was more comprehensive, being part of a universal health care system. Bernstein et al included all cases of isotretinoin use prior to IBD diagnosis, whereas Crockett et al examined cases in which isotretinoin was taken in the 12 months prior to IBD diagnosis; this temporal stringency may improve the case for causality. Furthermore, Crockett et al examined the effects of isotretinoin dose and exposure, whereas Bernstein et al. did not. Neither discussed recent or distant usage of antibiotics in their subjects. Finally, while Crockett et al state that acne was not independently associated with ulcerative colitis (UC) or IBD, they did not examine acne by severity/subtype, an important confounding factor.

Table IStudies examining the link between isotretinoin and IBD

Study design (authors, year) Outcome
Case-control study of IBD patients using the University of Manitoba IBD Epidemiology Database (Bernstein et al,5x5Bernstein, C.N., Nugent, Z., Longobardi, T., and Blanchard, J.F. Isotretinoin is not associated with inflammatory bowel disease: a population-based case-control study. Am J Gastroenterol. 2009; 104: 2774–2778
Crossref | PubMed | Scopus (84) | Google ScholarSee all References 2009)
2008 IBD cases
1.2% of IBD cases used isotretinoin before diagnosis compared with 1.1% of control subjects using isotretinoin (statistically insignificant). This is similar to the percentage of IBD patients who used isotretinoin after diagnosis (1.1%).
There was no difference when IBD was subdivided as CD and UC.
Inclusion criteria required that persons residing in the province for at least 2 years were designated as having IBD only if they had at least 5 separate physician claims and/or hospitalizations; persons residing in the province for less than 2 years were included in the IBD cohort if they had at least 3 separate physician claims and/or records.
Acne severity or its association with IBD was not addressed.
Mean number of days between the first isotretinoin prescription and initial IBD diagnosis for IBD patients who used isotretinoin before IBD diagnosis was 1102.4 days.
Case-control study of patients in the PharMetrics Patient-Centric Database (an American insurance claims database) (Crockett et al,6x6Crockett, S.D., Porter, C.Q., Martin, C.F., Sandler, R.S., and Kappelman, M.D. Isotretinoin use and the risk of inflammatory bowel disease: a case-control study. Am J Gastroenterol. 2010; 105: 1986–1993
Crossref | PubMed | Scopus (103) | Google ScholarSee all References 2010)
8189 IBD cases
UC strongly associated with isotretinoin exposure in the 12 months before diagnosis (OR: 4.36 ). UC was also associated with isotretinoin exposure in the 24 months before diagnosis (OR: 2.90 )
Risk of UC was highest in those cases exposed to isotretinoin for at least 60 days compared with nonusers (OR: 5.63 )
A diagnosis of acne was not independently associated with UC (OR: 1.25 ).
Inclusion criteria required that all subjects meet primary IBD definition (≥3 IBD diagnoses on separate dates or ≥1 IBD diagnosis and 1 IBD-specific medication) with at least 12 months of continuous enrollment prior to first IBD claim.
Although acne was not associated with UC, the authors never stratified/subtyped acne (eg, mild, moderate, or severe) to see if more severe acne was associated with UC.

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CD, Crohn disease; CI, confidence interval; IBD, inflammatory bowel disease; OR, odds ratio; UC, ulcerative colitis.

Table IISelf-reported questionnaire-based studies exploring the association between IBD and environmental factors

Study design (authors, year) Environmental factor (subset of total results) Outcome OR (95% CI) Limitations
Case-control multicenter self-administered questionnaire to IBD patients (Gilat et al,7x7Gilat, T., Hacohen, D., Lilos, P., and Langman, M.J. Childhood factors in ulcerative colitis and Crohn’s disease. An international cooperative study. Scand J Gastroenterol. 1987; 22: 1009–1024
Crossref | PubMed | Scopus (295) | Google ScholarSee all References 1987)
499 IBD cases
Antibiotics
Recurrent respiratory infections
Hospitalization for respiratory infections
CD
UC, CD
IBD
Not reported
1.58 (0.98-2.58)∗, 1.25 (0.85-1.89)∗
Not reported
∗Authors claim statistical significance but reported that confidence interval crosses 1.
No correction for making multiple comparisons. This increases the chance of a type 1 error where the null hypothesis is rejected when it is, in fact, true.
Case-control study of IBD patients from North Carolina with neighbor controls (Wurzelmann et al,8x8Wurzelmann, J.I., Lyles, C.M., and Sandler, R.S. Childhood infections and the risk of inflammatory bowel disease. Dig Dis Sci. 1994; 39: 555–560
Crossref | PubMed | Scopus (137) | Google ScholarSee all References 1994)
503 IBD cases
Penicillin exposure
Penicillin exposure after correction for frequency of infection
Childhood infections
CD
CD, UC
1.18 (0.98-3.31)∗
Not significant
4.76 (2.65-8.23)
2.37 (1.19-4.71)
∗Crosses the confidence interval of 1.
No correction for multiple comparisons
Case-control study of IBD patients recruited from public and private clinics and hospitals in Canterbury, New Zealand (Gearry et al,9x9Gearry, R.B., Richardson, A.K., Frampton, C.M., Dodgshun, A.J., and Barclay, M.L. Population-based cases control study of inflammatory bowel disease risk factors. J Gastroenterol Hepatol. 2010; 25: 325–333
Crossref | PubMed | Scopus (143) | Google ScholarSee all References 2010)
1291 IBD cases
Antibiotics given >4 times per year during adolescence
Appendectomy
Tonsillectomy
Infectious mononucleosis
Smoking
CD
CD, UC
CD
CD
CD, UC
1.89 (1.16-3.09)
1.57 (1.11-2.22), 0.41 (0.27-0.63)
1.37 (1.03-1.83)
1.64 (1.11-2.43)
1.99 (1.48-2.68), 0.67 (0.48-0.94)
No correction for multiple comparisons (102-item questionnaire)
Case-control study comparing 21 Belgian families having high prevalence of CD with 10 matched control families (Van Kruiningen et al,10x10Van Kruiningen, H.J., Joossens, M., Vermeire, S., Joossens, S., Debeugny, S., Gower-Rousseau, C. et al. Environmental factors in familial Crohn’s disease in Belgium. Inflamm Bowel Dis. 2005; 11: 360–365
Crossref | PubMed | Scopus (46) | Google ScholarSee all References 2005)
74 CD cases
Antibiotics
Appendicitis during adolescence
Skin disease
Smoking
Childhood respiratory infections
CD
CD
CD
CD
CD
No association
Not reported
2.71 (1.05-7.0)
Not reported
No associations
Only CD examined, not UC
Tertiary referral center
No correction for multiple comparisons (176-item questionnaire)

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CD, Crohn disease; CI, confidence interval; IBD, inflammatory bowel disease; OR, odds ratio; UC, ulcerative colitis.

Table IIIPopulation-based case-control studies examining the link between tetracyclines and IBD

Study design (authors, year) Drug Outcome OR (95% CI)
Retrospective case-control study of CD patients from a UK general practitioner database (Card et al,11x11Card, T., Logan, R.F., Rodrigues, L.C., and Wheeler, J.G. Antibiotic use and the development of Crohn’s disease. Gut. 2004; 53: 246–250
Crossref | PubMed | Scopus (109) | Google ScholarSee all References 2004)
587 CD cases
Antibiotic prescriptions during the preceding 2 to 5 years
Tetracycline∗∗
Metronidazole/tinidazole∗∗
Other antibiotics (penicillins, cephalosporins, macrolides, sulfonamides, quinolones)∗∗
Drugs other than antibiotics
Nicotine
CD
CD
CD
CD
CD
CD
1.32 (1.05-1.65)
1.33 (1.01-1.77)
1.71 (1.05-2.76)
No association
1.54 (1.38-1.70)
1.55 (1.22-1.98)
Database representing 5% of UK’s population containing diagnosis, treatment, and prescriptions data
Only CD
Associations existed not only for antibiotics but also for drugs in general (excluding antibiotics).
Acne severity not assessed
Retrospective population-based case-control study of CD in Sweden (Hildebrand et al,13x13Hildebrand, H., Malmborg, P., Askling, J., Ekbom, A., and Montgomery, S.M. Early-life exposures associated with antibiotic use and risk of subsequent Crohn’s disease. Scand J Gastroenterol. 2008; 43: 961–966
Crossref | PubMed | Scopus (71) | Google ScholarSee all References 2008)
1098 CD cases
For inpatient setting only:
Pneumonia <5 years old
Pneumonia >5 years old
Otitis media (inpatient) <5 years old
CD
Pediatric CD
Adult CD
CD
CD
3.54 (1.78-7.04)
2.74 (1.04-7.21)
4.94 (1.83-13.34)
No association
No association
Pneumonia diagnosis used a surrogate marker for antibiotic use.
Otitis media, often treated with antibiotics, was not associated with CD.
The possibility exists of reverse causality where the infection is rather the risk factor for CD.
Only CD
Retrospective population-based case-control study of pediatric CD in a Canadian province (Shaw et al,14x14Shaw, S.Y., Blanchard, J.F., and Bernstein, C.N. Association between the use of antibiotics in the first year of life and pediatric inflammatory bowel disease. Am J Gastroenterol. 2010; 105: 2687–2692
Crossref | PubMed | Scopus (226) | Google ScholarSee all References 2010)
36 pediatric CD cases
Antibiotics given at age <1 year:
>1 prescription given
2-4 prescriptions
>4 prescriptions
Pediatric CD
Pediatric CD
Pediatric CD
2.9 (1.2-7.0)
2.9 (1.1-7.8)
5.0 (1.3-18.9)
Only looks at antibiotics given during first year of life
For early-onset (<13 years of age) IBD; mean age 8.4 years
Only pediatric CD
Smaller sample size
Retrospective population-based case-control study from a UK general practitioner database (Margolis et al,12x12Margolis, D.J., Fanelli, M., Hoffstad, O., and Lewis, J.D. Potential association between the oral tetracycline class of antimicrobials used to treat acne and inflammatory bowel disease. Am J Gastroenterol. 2010; 105: 2610–2616
Crossref | PubMed | Scopus (98) | Google ScholarSee all References 2010)
94,487 young adults with acne followed up for more than 406,000 person-years (of whom 61.2% had previous exposure to tetracyclines)
Tetracyclines as a class
Tetracycline/oxytetracycline∗∗
Doxycycline∗∗
Minocycline∗∗
Tetracyclines as a class∗∗
Tetracycline∗∗
Doxycycline∗∗
IBD
IBD
IBD
IBD
UC
CD
CD
1.39 (1.20-1.90)
1.46 (1.03-2.07)
1.58 (1.02-2.46)
NS
NS
1.61 (0.995-2.63)
2.25 (1.27-4.00)
UK-based database with size, structure, and content similar to database used in study of Card et al
Only looked at tetracyclines and not at other medications
Data spanned up to 7-year period
Low rate of isotretinoin in population studied
Acne severity not assessed.

View Table in HTML ∗Subgroup analysis.

There may be an association between certain acne treatments and IBD, but there may simply be an association between severe acne and IBD,15x15McAuley, D. and Miller, R.A. Acne fulminans associated with inflammatory bowel disease. Report of a case. Arch Dermatol. 1985; 121: 91–93
Crossref | PubMed | Scopus (26) | Google ScholarSee all References two inflammatory entities occurring in the same age group. Furthermore, those persons taking isotretinoin and tetracyclines see physicians more frequently (and perhaps have a greater chance of receiving other medical diagnoses). In our practice, we discuss these possible associations with our patients when prescribing tetracyclines and isotretinoin, but mention that not all studies have demonstrated a link, that the absolute risk is low, that no study has demonstrated a causal association, and that acne may be associated with other inflammatory disorders.

More evidence ties acne drug to bowel disease

NEW YORK (Reuters Health) – Adding to evidence that the acne drug isotretinoin may lead to bowel disease in some users, a new study finds that patients on the medication were four times more likely than non-users to develop ulcerative colitis within a year.

Reporting in the American Journal of Gastroenterology, researchers say that the risk of any one isotretinoin user developing ulcerative colitis is “likely quite small.”

However, the findings do strengthen the evidence of a cause-and-effect relationship between the acne drug and inflammatory bowel disease (IBD) — a group of digestive disorders that includes ulcerative colitis and Crohn’s disease.

Isotretinoin, which is used to treat severe acne, is probably best known by the brand-name Accutane. That drug was taken off the market last year in the face of competition from generic alternatives — though in pulling the medication, maker Roche Pharmaceuticals also cited costs from defending personal-injury lawsuits.

Earlier this year, the company was ordered to pay $25 million in damages to a former Accutane user who claimed that the drug caused his IBD.

The company has maintained that there is no strong evidence that the acne drug triggers IBD. Between 1997 and 2002, 83 cases of IBD among isotretinoin users were reported to the U.S. Food and Drug Administration, but that does not prove that the drug itself is to blame.

For the new study, Dr. Seth D. Crockett and colleagues at the University of North Carolina Chapel Hill tried to test the cause-and-effect relationship.

Using a database of information from 87 U.S. health insurance plans, the researchers identified 8,189 people — mostly adults — who’d been diagnosed with IBD. They then compared each of those individuals with up to three other health plan members the same age and sex with no history of IBD.

Of the nearly 8,200 IBD patients, Crockett’s team found, 24 had used isotretinoin in the year before diagnosis; and of the nearly 22,000 controls, 36 had used the acne drug over a one-year period.

Overall, the researchers found, isotretinoin users were roughly four times more likely than non-users to have ulcerative colitis. There was no association, however, between isotretinoin use and Crohn’s disease.

The researchers also found that the risk of ulcerative colitis tended to climb in tandem with patients’ daily dose of the drug — which strengthens the case for a cause-and-effect relationship. There was no evidence that severe acne itself was linked to IBD risk.

Still, the findings do not definitively prove that isotretinoin was the cause of some patients’ ulcerative colitis, and the researchers say that further studies are needed to confirm their results.

If the acne drug does lead to ulcerative colitis in some cases, the absolute risk of that happening to any one patient are probably quite small, Crockett and his colleagues point out. But, they add, patients with severe acne should be aware of the possible link between isotretinoin and IBD before they are prescribed the drug.

The biological mechanism by which isotretinoin might contribute to IBD is not clear, but some researchers have speculated that the drug may affect immune function in the intestines. Both Crohn’s disease and ulcerative colitis are thought to involve abnormal immune system activity.

As for why isotretinoin was linked to ulcerative colitis, but not Crohn’s, in this study, Crockett and his colleagues point out that while the two disorders are related, they are distinct and have different immune-system-related features.

SOURCE: here 4a.html American Journal of Gastroenterology, online March 30, 2010.

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Common acne treatments linked to bowel problems

NEW YORK (Reuters Health) – Acne is a difficult enough burden for a young person to bear. Now there’s evidence that antibiotics commonly prescribed to help control severe breakouts may, in a very small number of patients, lead to inflammatory bowel disease.

Bowel disorders linked to acne treatment are “a rare outcome,” cautioned Dr. David Margolis, a dermatologist and lead author of a study in the American Journal of Gastroenterology, in an interview with Reuters Health.

Nonetheless, previous studies have suggested that the acne drug isotretinoin, known commonly by the brand name Accutane, might be the cause of inflammatory bowel disease in a small number of patients being treated for severe acne.

Noting that most people given isotretinoin have already been taking antibiotics for months, if not years, Margolis and colleagues at the University of Pennsylvania wanted to know if antibiotics might play a role in triggering the bowel condition.

Up to 90 percent of teenagers and young adults battle acne at some point. Drugs from the tetracycline family are the most commonly prescribed antibiotics for the treatment of severe acne.

“They limit scarring and the outbreak of pimples. They’re exceedingly effective and have been used for years,” Margolis said.

The researchers looked at the medical records of more than 94,000 British teenagers and young adults diagnosed with acne between 1998 and 2006.

They found that long-term use of antibiotics appeared to double the risk of developing inflammatory bowel disease in these subjects. Of the 207 cases of inflammatory bowel disease diagnosed among the 94,487 patients in the study, 152 (0.26 percent of all subjects) were taking one of three commonly prescribed tetracycline-based antibiotics and 55 (0.14 percent) were not.

Patients taking one of the three drugs, doxycycline, appeared to be at a slightly higher risk (0.21 percent) of developing an inflammatory bowel disease compared to patients taking minocycline (0.17 percent risk) or tetracycline (0.20 percent risk).

“The association was probably most pronounced in terms of Crohn’s disease, a subgroup,” Margolis said.

Crohn’s disease is an inflammation of the lining of the digestive tract, which can lead to abdominal pain, severe diarrhea and malnutrition. It affects an estimated 400,000 people in the U.S. Some 600,000 Americans suffer another inflammatory bowel disease, ulcerative colitis. Both are treated with anti-inflammatory drugs and some complications of the conditions can require surgery.

“This potential risk should be considered when prescribing this medication,” the authors write, while also urging more study of the connection between acne drugs and bowel disorders. It is possible, for instance, that the risk of inflammatory bowel disease is related to the biology of severe acne itself and not to treatments for it, they note.

“This is a rare outcome, rare enough you need to be careful about making decisions to change clinical practice,” Margolis said.

Inflammatory bowel diseases, such as Crohn’s disease and ulcerative colitis, can be life-altering conditions that restrict social interactions and increase depression.

Severe acne is also a “bad disease,” Margolis said. “These people have lots of concerns about their health, their appearance and how they function in society, and they are at an increased risk of depression,” Margolis pointed out.

Margolis was prompted to conduct the study after being asked to review records by lawyers representing a generic manufacturer of isotretinoin. The legal case is still in the discovery phase.

“I’m not sure if isotretinoin (Accutane) is on or off the hook all by itself,” he said. “I think this research indicates that in a careful study one should probably consider antibiotic use,” as well, he added.

SOURCE: American Journal of Gastroenterology, available online August 10, 2010.

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FAQs about Ulcerative Colitis

What is ulcerative colitis?

Ulcerative colitis is an inflammatory bowel disease of unknown cause in which the gastrointestinal tract is unable to distinguish foreign from self-antigens. It is characterized by chronic inflammation of the colonic mucosa and submucosa, atrophy and possibly dysplasia limited to the colon. The extent of disease varies and may involve only the rectum (ulcerative proctitis), the left side of the colon to the splenic flexure or the entire colon (pancolitis).

What causes ulcerative colitis?

Hereditary factors seem to play a role in the etiology of ulcerative colitis. The most significant risk factor for the development of ulcerative colitis is a family history. Environmental factors are also involved, as evidenced by higher rates of this disease in urban locales.

What are the symptoms of ulcerative colitis?

The most common symptom of ulcerative colitis is diarrhea that is often bloody. Other symptoms include abdominal and/or rectal pain, fever and weight loss. Some patients complain of constipation and rectal spasm. Arthritis symptoms may occur in as many as 26 percent of patients with ulcerative colitis, dermatological changes in fewer patients and ocular manifestations in about 5 percent.

How is ulcerative colitis diagnosed?

The disease is diagnosed using clinical presentation, CT scans, endoscopy, and usually confirmed by endoscopic biopsy. Because the initial presentation of the disease is indistinguishable from other forms of acute colitis, diagnosis of ulcerative colitis should not be made until all infectious causes are ruled out and symptoms have persisted for at least two weeks. Barium enema is not necessary if all other forms of colitis are excluded and if it is believed that the disease is more than proctosigmoiditis.

Who is affected by ulcerative colitis?

Both sexes are equally affected, and there is a higher prevalence of the disease in Ashkenazi Jews. Heredity does play an important role in this disease. Approximately 10 percent of patients with UC have a first-degree relative with the disease. The peak onset for this disease is the second or third decade of life. A secondary peak is seen in late middle age.

Is there a relationship between smoking cigarettes and developing UC?

Data from population surveys indicate that patients with ulcerative colitis are less likely to be smokers than matched controls from the general population. The relative risk of developing ulcerative colitis among current smokers is about 40 percent. Former smokers are about 1.7 times more likely to develop the disease than those who have never smoked. Recent controlled trials of nicotine patch therapy for ulcerative colitis suggest that nicotine may play a role in preventing the disease. There have been anecdotal reports of improvement in active stages when former smokers resumed smoking. However, other forms of medical therapy should be attempted and exhausted before resorting to this method. A high proportion of nonsmokers experienced unacceptable side effects from nicotine patches.

What is the treatment for ulcerative colitis?

The treatment for ulcerative colitis is targeted to active disease and then maintenance of remission. Medical and surgical modalities are used to treat ulcerative colitis. The majority of patients respond favorably to medical regimens. Surgery is reserved for those patients who are unresponsive to medical therapy and have a severely compromised quality of life.

Will I eventually need to have surgery for ulcerative colitis?

If acute colitis does not respond to intensive medical therapy, surgery may be considered. Patients who have had this disease for eight to 10 years and are steroid resistant or dependent have an increased risk of colon cancer and should consider colectomy.

What type of surgery is done for ulcerative colitis?

Current surgical alternatives for patients include total proctocolectomy with Brooke ileostomy, intra-abdominal Koch pouch and restorative proctocolectomy with ileal pouch-anal anastomosis. Elective colectomy cures ulcerative colitis and has a very low mortality.

What is pouchitis?

Pouchitis is a nonspecific acute or long-term inflammation of the pouch formed during surgery. The cause is uncertain, but the risk of developing pouchitis is greater in patients with chronic ulcerative colitis.

How common are extraintestinal manifestations of ulcerative colitis?

The minor extraintestinal manifestations of ulcerative colitis, such as canker sores, joint pain and tender lumps on the legs, are common and tend to accompany flare-ups. Arthritis complications occur in about 25 percent of patients. Dermatological changes are commonly associated with this disease. Ocular manifestations occur in 5 percent of patients with extensive disease. In most situations, extraintestinal manifestations respond to medical therapy.

How does diet affect the management of ulcerative colitis?

It is important, especially in children, to maintain a healthy, balanced nutritional intake. No general dietary recommendations exist, except for the avoidance of milk and milk products for patients with lactose intolerance. Common sense suggests that foods prone to induce more frequent bowel movements, such as caffeine, alcohol, red pepper and laxative fruits (prunes, fresh cherries and peaches), should be avoided. In patients with proctitis and constipation, added bulk in the form of psyllium or bran may be helpful.

Does stress play a role in causing or exacerbating symptoms?

There has been no evidence correlating disease activity with personality type, personal history or stressful life events. Additionally, there has been no evidence of definable mental illness in patients with ulcerative colitis as compared with patients comparably ill with other forms of intestinal disease.

How will this disease change my life?

The effects of any long-term illness can be emotionally and physically draining. Learning to live with the unpredictable flare-ups, pain and diarrhea can be especially difficult for some patients. Patients with ulcerative colitis can lead a relatively normal life, however, with effective medical therapy.

6 Skin Conditions Associated With Ulcerative Colitis

If you do notice any skin changes, it’s important to tell your doctor right away so you can be seen by a dermatologist, says Kally Papantoniou, MD, a clinical assistant professor of dermatology at Mount Sinai Hospital in New York City.

Ulcerative Colitis and Your Skin

Skin conditions that you may be susceptible to along with ulcerative colitis include:

1. Erythema nodosum. This rash consists of painful, raised bumps that are usually found on the legs, Dr. Hagan says. It tends to develop when ulcerative colitis is active, she adds. You may also run a fever, have joint pain, and generally feel ill, according to the National Library of Medicine.

Treatment options include pain-relieving medications, steroids (taken either by mouth or injection), and potassium iodide solution to clear up the bumps.

“A cool compress can also help alleviate discomfort and reduce inflammation,” Dr. Papantoniou says, adding that elevating your legs may help lessen swelling and tenderness. Compression stockings may help as well, but have your doctor evaluate you for vascular disease before using them, she cautions.

Symptoms usually go away within about six weeks, but they may come back.

2. Pyoderma gangrenosum. This rash, which spreads quickly, is made up of red or purple bumps or blisters. They eventually join together and form deep open sores (ulcers) with a blue or purple border, according to the National Organization for Rare Disorders (NORD).

The ulcers can occur almost anywhere: “People can have them on their feet, making it difficult to walk,” Hagan says. “They can have them on their legs, or their stomachs.” Sometimes the rash develops around the site of an injury or surgical wound.

Unlike erythema nodosum, this skin problem often appears when bowel disease is quiet, Hagan says. It also can be difficult to treat, she adds.

“Pyoderma gangrenosum can leave terrible scars,” says Joaquin Brieva, MD, a dermatologist at Northwestern Memorial Hospital in Chicago. The condition requires sophisticated wound care by an expert team plus treatment for the underlying colitis.

Treatments include medicines that target the skin or whole-body therapies, such as anti-inflammatory creams and steroid ointments; steroids pills or injections, which are sometimes injected directly into the ulcers; and medications that suppress the immune system.

3. Aphthous stomatitis. Also known as canker cores, these are white spots with a red base that are found in the lining of the mouth or on the tongue, Hagan says. Some people get them right before a flare, she adds.

In people with ulcerative colitis, canker sores are often larger than a centimeter and hang around longer than 2 weeks, Dr. Brieva says.

Treatment includes tetracycline mouthwashes, steroid medications that are made to stick to the mouth and gums, and lidocaine, among other things, he adds.

According to the National Library of Medicine, you can also try to:

  • Suck on something cold, like an ice pop.
  • Swish milk of magnesia around your mouth to coat the sore, and then spit it out.
  • Mix a half-cup of salt into a cup of water and rinse your mouth with an ounce of the mixture four times a day.

4. Pyoderma vegetans. This is a rare condition that appears as blisters, plaques, or patches around the groin and under the arms, according to the Crohn’s & Colitis Foundation of America (CCFA). Pyostomatitis vegetans is the same condition, but it occurs in the mouth, Brieva says. Treatment for this skin condition typically just involves treating the ulcerative colitis itself.

5. Sweet’s syndrome. This is another rare skin complication linked to ulcerative colitis, according to NORD. It comes with a fever and a rash made up of many tender red or bluish-red bumps or spots. They usually develop on the arms, legs, torso, face, or neck. Arthritis and eye inflammation are sometimes symptoms, too. Sweet’s syndrome is usually treated with steroids.

6. Clubbing. In this condition, the skin underneath your fingernails thickens and the fingertips become rounded and fat, like the tip of a drumstick, Brieva says. Your nails also curve over your fingertips. There’s no treatment for clubbing, according to the CCFA.

What to Do

There’s really nothing you can do to prevent any of these skin conditions related to ulcerative colitis, Hagan says.

However, stress can bring on a flare of ulcerative colitis, and it’s possible that a flare can worsen related skin conditions, too. “Meditation or deep breathing may be very helpful in reducing stress,” Papantoniou adds.

To minimize the outward appearance of skin problems, try covering up problem areas with clothes if you can — and makeup is okay in some cases. “As long as the skin barrier isn’t broken, it’s safe to cover up hyperpigmentation or red patches with a concealer,” Papantoniou says. Ask your healthcare provider which products are safe for you to use.

Oral manifestations of inflammatory bowel disease

What is inflammatory bowel disease?

There are two main forms of inflammatory bowel disease – ulcerative colitis and Crohn disease. Both are characterised by abdominal pain and diarrhoea, sometimes with bleeding.

  • Ulcerative colitis typically involves only the colon (large bowel)
  • Crohn disease can affect any part of the gastrointestinal tract from the lips to the anus with scattered lesions. Crohn disease is characterised on pathology by non-caseating granulomas but these are not always found on bowel biopsy.

Although the two diseases are quite separate, accurate diagnosis can sometimes be difficult especially in the early stages. Therefore involvement of other organs can help to make the distinction.

Involvement of body sites other than the bowel in inflammatory bowel disease

Both forms of inflammatory bowel disease can develop symptoms and signs in addition to the bowel disease. Changes in the skin and oral mucosa can develop with both, but are more commonly seen with Crohn disease. Sometimes these develop before the diagnosis of inflammatory bowel disease, leading the doctor to investigate for bowel problems. In some patients they may appear with flares of the bowel inflammation. Where the association is specific with diagnostic histology, it can be valuable in making the diagnosis.

Oral mucosa signs of inflammatory bowel disease

The changes of the face and oral mucosa associated with inflammatory bowel disease can be divided into four main categories:

  1. Specific, meaning these occur only in association with the bowel disease and/or show characteristic histology of that condition.
  2. Non-specific, meaning these occur more commonly with the bowel disease than in the general population, but also do occur without bowel disease, and the pathology is not diagnostic for the bowel disease.
  3. Complications of malabsorption caused by the bowel inflammation resulting in deficiencies in vitamins and minerals.
  4. Side effects or complications of medications prescribed to treat the bowel disease.

The first three of these categories may be useful in directing the doctor to the bowel problem and making the specific diagnosis.

Oral signs of Crohn disease

The oral mucosa is commonly affected in Crohn disease with up to one third of patients reported to have oral changes, and even higher in children. In some studies, the oral changes preceded the diagnosis of Crohn disease in 60%. There may be a male predominance.

1. Specific oral mucosal changes: orofacial Crohn disease

In children with Crohn disease, orofacial Crohn disease can be an important presentation preceding the bowel diagnosis.

2. Nonspecific changes in the mouth and surrounding facial skin associated with Crohn disease:

  • Angular cheilitis
  • Aphthous ulcers/aphthous stomatitis – has been reported to affect up to 20-30% of patients with Crohn disease, although some studies show no increase in this compared to the general population. These cannot be distinguished clinically from the common aphthous ulcers.
  • Recurrent abscesses
  • Redness and scaling around the lips
  • Pyostomatitis vegetans – very rare in Crohn disease
  • Dry mouth – can result in dental decay, denture discomfort and infection
  • Bad breath (halitosis)
  • Recurrent vomiting and regurgitation can cause oral pain and the acid result in dental decay.

Oral signs of ulcerative colitis

Mucosal changes have been reported in some patients with ulcerative colitis.

1. Specific orofacial changes of ulcerative colitis: pyostomatitis vegetans

2. Nonspecific changes of the mouth and surrounding skin associated with ulcerative colitis:

  • Minor and major aphthous ulcers/stomatitis – reported in at least 10%, usually worse with flares of the bowel disease and improving with treatment of the bowel inflammation. However this is probably no more common than the general population.
  • Glossitis (inflamed tongue)
  • Cheilitis (inflamed lips)
  • Bad breath (halitosis)

In children with ulcerative colitis, only nonspecific changes were seen in one large study.

Orofacial signs of malabsorption

Malabsorption may be due to the chronic diarrhoea, reduced food intake, overgrowth of bacteria in the bowel, bowel surgery, the disease itself, or the drugs used to treat the bowel disease.

  • Folic acid deficiency (Crohn disease as absorbed from small bowel) – red painful tongue (acute), becomes shiny and smooth (chronic) (glossitis), and cracked lips (cheilitis).
  • Iron deficiency
  • Zinc deficiency – acrodermatitis enteropathica, oral candidiasis, glossitis
  • Zinc deficiency – acrodermatitis enteropathica (DermNetNZ), oral candidiasis (thrush), glossitis
  • Vitamin A deficiency – white patches on oral mucosa due to keratinization of mucous membranes
  • Vitamin B complex deficiency – stomatitis-glossitis-angular cheilitis
  • Riboflavin (vitamin B2, Crohn disease as absorbed from small bowel) – cheilosis, angular cheilitis, glossitis
  • Niacin (vitamin B3) deficiency – pellagra
  • Vitamin B12 deficiency (Crohn disease as absorbed from small bowel) – glossitis (beefy red tongue with flat red patches mainly on the sides and top of the tongue), angular cheilitis, mouth ulcers, oral candidiasis, diffuse erythematous mucositis, pale oral mucosa, soreness of the tongue or mouth, burning mouth, reduced taste sensitivity
  • Vitamin C deficiency – scurvy
  • Vitamin K deficiency – gum bleeding

Orofacial changes due to medications used to treat inflammatory bowel disease

Many different medications may be used to treat various aspects of inflammatory bowel diseases including antibiotics, biologic agents, immunosuppressants, anti-diarrhoeal agents and for pain. An alphabetical listing of some of the more common treatments follows, with their oral side effects.

Medication Adverse effects
adalimumab (biologic) infections, angioedema
Budesonide (oral steroid) glossitis, swelling of the tongue, dry mouth
Certolizumab (biologic) Stevens-Johnson syndrome / toxic epidermal necrolysis, angioedema
Cholestyramine (anion exchange resin) irritation of the tongue, sour taste, dental bleeding, dental caries, erosion of tooth enamel, tooth discoloration
Ciclosporin (calcineurin inhibitor) gum hyperplasia
Ciprofloxacin (antibiotic) oral candidiasis, angioedema, Stevens-Johnson syndrome / toxic epidermal necrolysis, loss of taste
Colestipol (anion exchange resin) difficulty swallowing
Diphenoxylate and atropine (antispasmodics) dry mouth, lip swelling, taste changes or loss
Infliximab (biologic) infections, angioedema
Loperamide (antidiarrhoeal) dry mouth, Stevens-Johnson syndrome / toxic epidermal necrolysis, angioedema
Mesalazine (anti-inflammatory) sore throat, oral candidiasis, dry mouth, stomatitis, altered taste
Methotrexate (folic acid antagonist) stomatitis, gingivitis, pharyngitis
Metronidazole (antibiotic) unpleasant metallic taste, furry tongue, glossitis, stomatitis, oral candidiasis, dry mouth
Prednis(ol)one (oral steroid) oral candidiasis (thrush)
Propantheline (antispasmodic) dry mouth, angioedema, loss of taste
Sulphasalazine (anti-inflammatory) stomatitis, Stevens-Johnson syndrome / toxic epidermal necrolysis, altered taste, impaired folic acid absorption
Tacrolimus (calcineurin inhibitor) oral candidiasis, aphthous mouth ulcers, Stevens-Johnson syndrome / toxic epidermal necrolysis, angioedema

Azathioprine and mycophenolate mofetil, often used to treat inflammatory bowel disease, do not have reported side effects in the mouth.

Skin Complications of IBD

After arthritis, skin disorders represent the next most common extraintestinal complication of IBD. These affect about 5% of people with inflammatory bowel disease.

SKIN DISORDERS COMMONLY SEEN IN IBD

ERHTHEMA NODOSUM

The name literally means “red bumps.” These tender red nodules, which usually appear over the shins or ankles and sometimes on the arms, occur most in people with ulcerative colitis (2%-4%), although they may also affect those with Crohn’s disease of the colon (1%-2%). Women are more commonly affected than men. Erythema nodosum generally appears in conjunction with a flare-up of IBD, but it also may occur just before a flare-up. It tends to improve when the bowel disease is brought under control.

PYODERMA GANGRENOSUM

This condition is marked by pus in the skin associated with deep ulcerations. Like erythema nodosum, pyoderma gangrenosum is most often found on the shins or ankles but sometimes occurs on the arms, too. Beginning as small blisters, these lesions eventually join together to form into deep,chronic ulcers. The disorder is somewhat more common among people with ulcerative colitis (5%) than those with Crohn’s disease (1%). Pyoderma gangrenosum often follows a similar course to the pattern of the IBD itself, and may heal as the symptoms of IBD are brought under control. Antibiotics, injections of medications into the ulcers, and topical ointments all may be used as treatments.

ENTEROCUTANEOUS FISTULAS

A fistula is a small tunnel connecting two parts of the body. An enterocutaneous fistula is an abnormal channel from the intestine to the skin—often from the rectum to the vagina, bladder, or buttocks. It also may be a complication of surgery. This type of fistula may leak pus or fecal matter. Fistulas are more common in Crohn’s disease than in ulcerative colitis, affecting approximately 30% of people with Crohn’s. Treatment depends on the location and severity of fistulas.

SKIN TAGS

Skin tags are fairly common in people with Crohn’s disease. They develop around hemorrhoid swellings in and around the anus. When the swellings go down, the skin around them thickens and forms into small flaps. Fecal matter may attach to skin tags, irritating the skin. Practicing good hygiene will help reduce discomfort and calm the irritation. Surgical removal of skin tags should be avoided because of the risk of damage or scarring the anal sphincter or the anal canal itself.

ANAL FISSURES

These are small tears in the lining of the anal canal. They may crack and bleed, causing pain and itchiness. Warm baths and topical ointments may be helpful.

APHTHOUS STOMATITIS

These small mouth ulcers, also known as canker sores, are most often found between the gums and lower lip or along the sides or base of the tongue. They are usually seen during severe flare-ups of IBD and generally subside as the bowel disease comes under control. Medicinal mouthwashes may be helpful, along with a balanced diet and a multivitamin/mineral supplement.

SKIN DISORDERS INFREQUENTLY SEEN IN IBD

ACRODERMATITIS ENTEROPATHICA

Severe cases of IBD may produce other skin disorders associated with nutritional deficiencies. For example, people who have chronic diarrhea may lose zinc in their stool. This zinc deficiency may lead to acrodermatitis enteropathica, a flaky rash that generally appears on the face, hands, feet, and perineum. Various vitamin deficiencies also may produce skin manifestations such as bleeding or swollen gums and a flaky rash. These problems are less common today because of the increased attention to the importance of good nutrition in chronic illnesses such as IBD.

PYODERMA VEGETANS and VASCULITIS are other rare skin disorders, believed to be due to abnormal immune system activity.

  • Pyoderma vegetans, which affects people with ulcerative colitis, appears as blisters, plaques, or patches around the groin and under the arms. These become darkened areas of skin as they heal.
  • Vasculitis, which means “inflammation of the blood vessels,” is marked by raised reddened areas, sometimes ulcerous.

Treatment of both these disorders centers on treatment of the IBD itself.

EPIDERMOLYSIS BULLOSA ACQUISTA

This may develop in people who have had Crohn’s disease for many years. It is a blistering condition that appears on the knees, elbows, hands, and feet.

VITILIGO (marked by areas of decreased pigmentation) and PSORIASIS (a scaly, itchy disease) are occasionally linked with IBD, as is CLUBBING (in which the skin beneath the nails becomes thickened). The first two may respond to ultraviolet light therapy and oral medications. There is no treatment for clubbing.

DRUG REACTIONS

In some cases, a skin disorder is a result not of the IBD itself but rather of the medications used to treat the IBD.

  • Sulfasalazine, for example, may produce an allergy-type skin rash in some people. The reaction is attributed to the sulfa component of this agent. Newer medications—including mesalamine (Asacol®) and olsalazine (Dipentum®)—are similar to sulfasalazine but are manufactured without the sulfa ingredient.
  • Steroids also may cause skin problems when used on a long-term basis. These include stria or stretch marks, thinning of the skin, aggravation of acne, facial puffiness, ankle swelling, and slow wound healing.

For further information, call Crohn’s & Colitis Foundation’s IBD Help Center: 888.MY.GUT.PAIN (888.694.8872).

The Crohn’s & Colitis Foundation provides information for educational purposes only. We encourage you to review this educational material with your health care professional. The Foundation does not provide medical or other health care opinions or services. The inclusion of another organization’s resources or referral to another organization does not represent an endorsement of a particular individual, group, company or product.

How to Handle Skin Rashes Due to Ulcerative Colitis

Here’s a rundown of some skin issues you might encounter along with UC.

While the name would be a strong one for a death metal band, it actually refers to the most common UC-related skin rash, which affects 3 to 10 percent of peeps with the condition. Women get it more often than men.

Erythema nodosum appears as tender, red bumps, which can pop up in multiple areas of your body. They may show up during a UC flare-up and disappear along with the other symptoms.

The second most common UC-related skin condition is pyoderma gangrenosum (not a Harry Potter spell).

This condition is rare and presents as a blister forming on your arms, shins, or ankles. The classic type forms a characteristic ulcer. Pyoderma gangrenosum might be due to bodily trauma, such as having a biopsy or puncture to a vein, or an autoimmune response.

Pyoderma gangrenosum is treated with high doses of corticosteroids and immunosuppressants. Painful wounds may also be treated with prescription pain meds.

3. Sweet’s syndrome

Experts aren’t sure what causes Sweet’s syndrome, another rare skin condition, but it might be related to IBD, among other conditions. It commonly shows up as a painful, red “juicy” plaques on your arms, head, neck, and upper back.

In addition to IBD, risk factors for Sweet’s syndrome include cancers such as leukemia, an upper respiratory infection, pregnancy, and a sensitivity to certain medications.

Sweet’s can be treated with oral corticosteroids, but it often comes back.

4. Bowel-associated dermatosis-arthritis syndrome

So close to being abbreviated as BADASS but not deserving of such an acronym, this condition causes small, painful bumps on your chest and upper arms that may become pus-filled.

Researchers suspect inflammation somehow causes BADAS, aka “bowel bypass syndrome,” and it may stem from intestinal surgery, diverticulitis, or appendicitis in addition to IBD.

BADAS may accompany a UC flare-up and usually goes away on its own, but your doctor might prescribe corticosteroids and/or antibiotics.

5. Plaque psoriasis

Don’t blame your parents yet, but some studies link genetics to IBD and psoriasis. The association is more pronounced in people with Crohn’s disease.

Psoriasis is a chronic disorder that speeds up skin cell production, causing cells to build up in dry, flaky, rough, and red plaques that can sometimes be itchy. Plaque psoriasis is the most common form.

Psoriasis can show up almost anywhere on your body, including your nails, joints, and genitals. While there’s no cure, you can manage it with treatments like topical medications, immunosuppressants, biologics, and/or light therapy.

6. Vitiligo

Scientists have linked a specific gene to vitiligo — the same gene that’s associated with a higher risk of autoimmune disorders.

Vitiligo is a skin condition in which your immune system destroys skin cells responsible for pigment production (called melanocytes). This results in patches of skin lacking color.

It’s more common in people with UC and Crohn’s but can affect anyone. It isn’t contagious or painful, but people with vitiligo are more prone to sunburn and eye problems.

7. Plaques from pyodermatitis vegetans

This condition is characterized by red, scaly, and ulcerated plaques. It usually shows up in skin folds like those near your armpit and groin, or on your scalp and face.

It’s linked to pyostomatitis vegetans, a similar condition that causes pustules in your mouth. The two conditions combined are known as pyodermatitis-pyostomatitis vegetans or PPV.

PPV is closely linked to UC — so much so, in fact, that many people are diagnosed with UC only after first being diagnosed with PPV. But pustules typically form after UC has been present for a few years.

8. Leukocytoclastic vasculitis

“Leukocytoclastic vasculitis” (LCV) is a fancy dermatology term that refers to inflammation in the small blood vessels of your skin.

It characteristically appears as crops of small, raised, red-purplish spots on your legs. It can be seen in a number of medical conditions, and UC is one of them.

9. Hives

Breaking out in hives isn’t a symptom of UC, but some medications might cause them.

In rare cases, folks who take the biologic drug Humira for severe UC could have an allergic reaction that causes hives. Sulfasalazine is another UC treatment that might cause hives and skin rashes.

If you’re experiencing hives and you suspect a medication is the culprit, talk to your doctor ASAP about possible alternatives.

What about acne?

There is no direct relationship between UC and acne. However, oral corticosteroid medications, which are often prescribed to treat UC symptoms, can cause steroid acne.

Some acne medications may also contribute to the development of UC. A 2010 study linked the acne drug isotretinoin, aka Accutane, to an increased risk of UC.

The authors noted that people who have taken higher doses of Accutane seemed to have a slightly higher risk of developing UC than people who hadn’t used the medication. No connection to Crohn’s Disease was found.

A 2015 research review, however, didn’t support a causal relationship. The authors noted that people often have UC for a while without knowing it and that the condition was likely present before they started taking Accutane.

Skin signs of gastrointestinal disease

Introduction

Dermatological symptoms and signs sometimes precede or accompany a gastrointestinal disease. It should be noted that the embryonic origin of the gastrointestinal tract and the skin are closely aligned.

Liver cirrhosis

Common cutaneous manifestations of liver cirrhosis include:

  • Telangiectases
  • Spider telangiectasis
  • Palmar erythema
  • Terry nails (82%): white proximal (leukonychia) and pink distal nail plate.
  • Haemochromatosis: an autosomal dominant iron-accumulation disorder that may cause generalised bronze hyperpigmentation
  • Wilson disease: an autosomal recessive disorder of copper metabolism. Signs of Wilson disease include:
    • Kayser-Fleisher ring around iris
    • Pigmentation over the shins
    • Blue lunulae (half-moons) on nails
Cutaneous effects of liver disease

Nutritional and metabolic disorders

Nutritional deficiency

Malnutrition associated with deficiencies of fat-soluble and water-soluble vitamins often affects the skin.

Fat-soluble vitamins:

  • Vitamin A deficiency causes phrynoderma, ie keratotic follicular papules on anterolateral thighs and posterolateral upper arms.
  • Vitamin D deficiency in babies and children results in delayed tooth eruption with poor enamel. In adults, it predisposes to caries.
  • Vitamin K deficiency affects coagulation, leading to haemorrhage, purpura and ecchymoses.

Water-soluble vitamins:

  • Acute vitamin B2 deficiency results in:
    • Deep red erythema
    • Stomatitis
    • Epidermal necrolysis (peeling skin)
  • Chronic vitamin B2 deficiency causes:
    • Angular cheilitis
    • Prominent lingual papillae (papules on the tongue)
    • Seborrhoeic dermatitis
  • Vitamin B3 deficiency causes pellagra, characterised by:
    • Photosensitivity
    • Casal necklace – distribution around neck/upper chest
    • Cheilitis, glossitis (inflamed tongue), angular cheilitis, oral or perirectal ulcers
  • Vitamin B6 deficiency causes:
    • Seborrhoeic dermatitis-like eruption
    • Glossitis
    • Angular cheilitis
  • Vitamin B9/B12 deficiency is associated with:
    • Angular cheilitis
    • Hunter glossitis (atrophic, red and painful tongue)
    • Hair depigmentation
    • Hyperpigmentation (diffuse and symmetrical pigmentation, hands, nails, face, palmar creases, flexural regions and pressure points)
  • Vitamin C deficiency causes scurvy, characterised by:
    • Enlarged, hyperkeratotic hair follicles on posterolateral aspects of arms
    • Abnormal hair development
    • Swelling of gums, erythema
    • Splinter haemorrhage in nails
  • Biotin deficiency results in:
    • Periorificial dermatitis
    • Alopecia
    • Intertrigo and seborrhoeic erythroderma
Skin signs of vitamin deficiency

Acrodermatitis enteropathica

Acrodermatitis enteropathica is an autosomal recessive inherited form of zinc deficiency that manifests in infancy. It presents with the clinical triad of dermatitis, alopecia and diarrhoea. Skin signs include:

  • Pink, scaly patches and plaques on extremities, periorificial and anogenital sites
  • Can include psoriasiform plaques, vesicular, bullous, pustular or erosive lesions.
  • Hair loss may follow.

Eruptive xanthomas

Eruptive xanthomas are:

  • Caused by the accumulation of fat in macrophage cells in the skin
  • Associated with hypertriglyceridaemia, often due to diabetes mellitus

Dermatitis herpetiformis

Dermatitis herpetiformis is associated with:

  • Human leukocyte antigens (HLA) DQ2 or DQ8
  • Gluten-sensitive enteropathy (coeliac disease) with villous atrophy of duodenum

Skin signs of dermatitis herpetiformis include:

  • Intensely itchy herpetiform vesicles within erythematous or urticated plaques
  • Excoriated erythematous, crusted, grouped papules
  • Symmetrical distribution on extensor surfaces: elbows, knees, shoulders and buttocks

Inflammatory bowel disease

Inflammatory bowel disease (IBD) refers to ulcerative colitis and Crohn disease. There are similarities and differences in their cutaneous manifestations.

Oral aphthous ulcers

Aphthous ulcers are common in both forms of inflammatory bowel disease.

  • Round, oedematous mucosal ulcers
  • Sometimes associated with nutritional deficiencies
Aphthous ulceration

Erythema nodosum

Erythema nodosum (EN) is the most common skin sign of Crohn disease (4-6%) or ulcerative colitis (3%).

  • A form of panniculitis
  • Tender red subcutaneous nodules
  • Mostly on symmetrical extensor surfaces of lower legs
  • Can be found on thighs, extensor surfaces of arms, trunk and face
Erythema nodosum

Pyoderma gangrenosum

Pyoderma gangrenosum (PG) affects 0.7% of patients with Crohn disease and 2% with ulcerative colitis.

  • Ulcers with irregular undermined or overhanging necrotic borders
  • Usually affects lower extremities but may arise anywhere
  • Peristomal PG develops two months to 25 years after stoma creation
  • Associated with pyostomatitis vegetans: pustules and ulcers on lips and buccal mucosa.
Pyoderma gangrenosum

Perianal fissure/fistulae

Fissures and fistulae are common in Crohn disease (36%) and do not occur in ulcerative colitis.

  • Multiple circumferential fissures/fistulae

Swelling of oral cavity/labia

Mucosal oedema affects 8–9% of patients with Crohn disease and is absent in ulcerative colitis.

  • Frequently painful and disruptive to eating

Metastatic Crohn disease

Metastatic Crohn disease may cause cutaneous granulomatous plaques, nodules and ulcers.

  • Affects extremities or intertriginous areas
  • Facial and genital lesions are rare

Epidermolysis bullosa acquisita (EBA)

Epidermolysis bullosa acquisita (EBA) is a rare immunobullous disorder sometimes associated with Crohn disease.

Epidermolysis bullosa acquisita

Cutaneous polyarteritis nodosa

Cutaneous polyarteritis nodosa is a rare form of necrotising, small and medium-sized vasculitis.

  • 10% of cases are associated with IBD
  • Causes tender arterial nodules, palpable purpura and ulceration
  • Mainly affects lower extremities

Acute neutrophilic dermatosis

Acute neutrophilic dermatosis, also known as Sweet syndrome, is an autoinflammatory disorder sometimes associated with inflammatory bowel disease. Features include:

  • Fever and malaise
  • Cutaneous and mucosal involvement
  • Tender, oedematous erythematous papules and plaques
  • Vesicles, bullae or pustules within the plaques
  • Typically affects the head, neck and extremities but can be widespread
  • Usually resolves spontaneously within 5–12 weeks
Acute febrile neutrophilic dermatosis

Vascular disorders

Henoch-Schonlein purpura

Henoch-Schonlein purpura (HSP) is an immunoglobulin A-mediated, leukocytoclastic, small-vessel vasculitis.

  • Palpable purpuric lesions usually affect buttocks and legs.
  • HSP may also cause gastrointestinal vasculitis causing abdominal pain and malaena, due to bowel wall oedema, haemorrhage, and rarely, bowel infarction, perforation and intussusception.
  • Other symptoms may include arthritis (80%), abdominal pain (50–75%) and nephritis (40%).
Henoch Schönlein purpura

Degos disease

Degos disease is small vessel angiopathy, thought to be due to dysregulation of interferon-alfa and the membranolytic attack complex. There are two variants: benign atrophic papulosis and malignant atrophic papulosis.

  • Degos disease presents with 2–5 mm, rose-coloured papules that heal as umbilicated scars with white porcelain centre, erythematous rim, and surrounding telangiectasia.
  • Lesions most commonly occur on the trunk and arms, sparing the face, palms and soles.
  • Malignant atrophic papulosis is associated with gastrointestinal disease in 50–61%, causing intestinal perforation. Plaques are found on serosa and peritoneum.
Malignant atrophic papulosis

Hereditary haemorrhagic telangiectasia

Hereditary haemorrhagic telangiectasia (HHT) is a hereditary, autosomal dominant, bleeding disorder.

  • Multiple, small punctate telangiectases affect 50% of patients by 30 years of age.
  • Telangiectases are predominantly found on face and mouth.
  • Recurrent nosebleeds affect 90% of patients with HHT.
  • Bleeding may also occur from gastrointestinal arteriovenous malformations.
Hereditary haemorrhagic telangiectasia

Kaposi sarcoma

Kaposi sarcoma (KS) is a human herpesvirus 8-associated tumour of endothelial cells.

  • It presents with pink, red, brown or violaceous macules, papules, nodules or plaques.
  • These most often arise on lower extremities or head and neck.
  • KS often affects oropharynx, presenting as one or more violaceous stains on the hard palate.
Kaposi sarcoma

Blue rubber bleb naevus syndrome

Blue rubber bleb naevi are venous malformations of skin and gastrointestinal tract.

  • They may form anywhere from the mouth to the anus, most commonly in the small bowel.
  • The “blue rubber nipple” is a blue-purple, soft, rubbery subcutaneous nodule that fills after compression.
  • Associated haemangiomas are tender macular lesions found on upper limbs, trunk, perineum.
Blue rubber bleb naevus syndrome

Pseudoxanthoma elasticum

Pseudoxanthoma elasticum (PXE) is an inherited disease in which there are calcification and fragmentation of elastin fibres in the skin and internal organs.

  • It presents in early teens with cutaneous changes.
  • Small yellow papules coalescing into cobblestone plaques are found on neck, flexures, bottom lip and are associated with loss of cutaneous elasticity.
  • Gastrointestinal haemorrhage affects 15% of patients.
Pseudoxanthoma elasticum

Ehlers-Danlos syndrome type IV

Ehlers-Danlos syndrome (EDS) type IV is an inheritable connective tissue disease due to a defect in collagen synthesis.

  • Patients present with translucent skin, varicosities, delayed wound healing and keloids.
  • They are susceptible to arterial rupture and visceral perforation.
Ehlers-Danlos syndrome

Klippel-Trenaunay-Weber syndrome

Klippel-Trenaunay-Weber syndrome presents in infancy with a cutaneous capillary vascular malformation.

  • Vascular lesions start as salmon pink patches that deepen in colour and thickness over time.
  • Extensive varicose veins may lead to chronic venous insufficiency and lymphoedema.
  • Gastrointestinal involvement includes vascular malformation in jejunum, distal colon and rectum, and oesophageal varices.
  • Bony and soft tissue hypertrophy are common.
Capillary vascular malformations

Bowel-associated dermatosis-arthritis syndrome

Bowel-associated dermatosis-arthritis syndrome (BADAS, bowel bypass syndrome) presents with recurrent and episodic flu-like symptoms, polyarthralgia and cutaneous lesions.

  • BADAS is thought to be driven by the overgrowth of bacteria in areas of an altered gastrointestinal tract, following surgery or inflammation.
  • Skin signs include:
    • Erythematous macules rapidly evolve into vesiculopustules and inflammatory papules. These regress over about a week.
    • Mainly found on extremities and upper trunk
    • Flares every 4–6 weeks
Skin rash associated with bowel bypass syndrome

Hermansky-Pudlak syndrome

Hermansky-Pudlak syndrome is a form of tyrosine-positive oculocutaneous albinism with autosomal recessive inheritance.

  • Pigment dilution of skin, hair and eyes is noted at birth.
  • Hermansky-Pudlak syndrome is rare outside Puerto Rico.
  • It is associated with granulomatous colitis.

Hereditary gastrointestinal tumours

Familial adenomatous polyposis

Gardner syndrome is a variant of familial adenomatous polyposis with numerous adenomatous polyps and mucocutaneous findings, such as:

  • Epidermoid cysts on face or extremities.
  • Lipomas
  • Desmoid tumours (10-14%), which are benign fibrous mesenchymal neoplasms. They are non-tender, well-circumscribed, firm, flesh coloured tumours located on the abdomen; intra-, extra- and within the abdominal wall. They can also occur on the shoulder, chest wall and inguinal area.
Skin lesions that might be associated with Gardner syndrome

Hereditary nonpolyposis colorectal cancer

Hereditary nonpolyposis colorectal cancer, also known as Lynch syndrome, is the most common hereditary cancer.

  • It is an autosomal dominant disorder, accounting for 3% of all colon cancers.
  • The Torre-Muir variant has most of the skin manifestations:
    • Sebaceous adenomas: yellow papules or nodules usually on the face
    • Sebaceous carcinoma, usually a yellow nodule on an eyelid that may ulcerate and invade
    • Multiple keratoacanthomas

Peutz-Jeghers syndrome

Peutz-Jeghers syndrome is a hamartomatous polyposis syndrome with autosomal dominant inheritance.

  • Mucocutaneous pigmentation affects 95%, with small melanocytic macules (lentigines) that appear during childhood.
  • The lentigines cluster around the mouth, nostrils, eyes, digits, hands, feet, and perianal region.
  • Facial lentigines may fade in adult life; oral-buccal pigmentation is usually permanent.

Cowden syndrome

Cowden syndrome, or multiple hamartoma syndrome, is characterised by skin lesions and polyposis coli.

Trichilemmomas are benign hamartomas of the outer sheath of hair follicles. They are:

  • Flesh-coloured, smooth papules
  • 1–5 mm in size
  • Predominantly on face, head, neck and hairline

Other skin lesions described in Cowden syndrome include:

  • Benign papillomas on the face, oral mucosa and acral surfaces
  • Cobblestone appearance within the mouth
  • Lipomas (30%)
  • Café au lait macules (9%)
  • Acral and plantar keratoses
  • Sebaceous hyperplasia
  • Fibromas
  • Haemangiomas
  • Scrotal and furrowed tongue
  • Neuromas
  • Xanthomas
  • Lentigines around the mouth, on hands, feet and genitals
  • Vitiligo
  • Acanthosis nigricans

Cowden disease

Bannayan-Riley-Ruvalcaba syndrome

The Bannayan-Riley-Ruvalcaba (BRR) syndrome is a rare germline mutation with hamartomatous polyposis, macrocephaly and mental retardation. Skin manifestations include:

  • Genital lentigines, the most specific finding
  • Facial papillomas
  • Vascular malformations
  • Lipomas
  • Multiple acrochordons (skin tags)
  • Acanthosis nigricans

Juvenile polyposis syndrome

Juvenile polyposis syndrome is a rare autosomal dominant disorder associated with hereditary haemorrhagic telangiectasia.

Neurofibromatosis

Neurofibromatosis is a common, autosomal dominant, a neurodermatosis characterised by:

  • Café-au-lait macules
  • Axillary and inguinal freckling
  • Dermal neurofibromas
  • Lisch nodules of iris
  • Systemic involvement, which can include gastrointestinal tumours

Cronkhite-Canada syndrome

Cronkhite-Canada syndrome is a sporadic syndrome that affects older adults. It presents with:

  • Nail dystrophy (98%)
  • Hair loss
  • Diffuse hyperpigmentation
  • Loss of taste
  • Intestinal polyps
  • Malabsorption

Paraneoplastic syndromes associated with gastrointestinal malignancies

Acanthosis nigricans

Acanthosis nigricans is associated with insulin resistance.

  • It is characterised by hyperpigmented, velvety, hyperkeratotic plaques.
  • These affect axillary, inguinal, neck folds, mammary, umbilical and anogenital regions.
  • In malignant disease, acanthosis nigricans can affect areola, digital web spaces, extensor sites and mucous membranes.
  • Acanthosis nigricans associated with malignancy arises spontaneously and is rapidly progressive.
  • Gastrointestinal adenocarcinoma can be responsible for acanthosis nigricans.

“Tripe palm” or palmoplantar keratoderma

Tripe palm is associated with malignant acanthosis nigricans.

  • The abnormal palms are characterised by epidermal thickening with wrinkled broadened mesh-like ridges bounded by deep grooves within palms and fingers.
Tripe palms are associated with acanthosis nigricans

Multiple seborrhoeic keratoses

The acute onset of multiple, eruptive seborrhoeic keratosis is known as the sign of Léser-Trelat.

  • Seborrhoeic keratoses initially erupt on the trunk, then on the extremities or face.
  • When associated with gastrointestinal adenocarcinomas, the sign of Léser-Trelat carries a poor prognosis.
Seborrhoeic keratoses

Acrokeratosis neoplastica

Acrokeratosis neoplastica is also known as Bazex syndrome and is different from Bazex-Dupré-Christol syndrome associated with basal cell carcinomas.

  • Acrokeratosis paraneoplastica is a rare, acral and psoriasiform dermatosis associated with cancers in upper respiratory and gastrointestinal tracts.

Glucagonomoa syndrome

Glucagonoma is a rare, glucagon-secreting, pancreatic, alpha cell tumour.

  • Glucagonoma is associated with necrolytic migratory erythema, a painful, pruritic, annular, erythematous eruption with central blisters, erosions, crusting and postinflammatory pigmentation.
Necrolytic migratory erythema due to glucagonoma

Tylosis

Tylosis is an autosomal dominant form of focal, non-frictional and nonepidermolytic, palmoplantar keratoderma.

  • It involves more than 50% of the surface of palms and soles.
  • Type A tylosis usually arises between 5 and 15 years of age; it is associated with oesophageal carcinoma at a later age.
  • Type B arises in the first year of life and is generally benign.
Focal palmoplantar keratoderma (areata type)

Plummer-Vinson syndrome

Plummer-Vinson syndrome is a rare triad of dysphagia, iron deficiency anaemia and oesophageal webs.

  • Plummer-Vinson syndrome is associated with oesophageal squamous cell cancer.
  • Skin signs include:
    • Brittle koilonychia (spoon-shaped, thin nail plates)
    • Oral leukoplakia due to intraepithelial carcinoma
    • Angular cheilitis
    • Pale, atrophic buccal mucosa
    • Glossitis
Iron deficiency

Extramammary Paget disease

Extramammary Paget disease is an intraepithelial adenocarcinoma located in and around the anal verge, vulva, or male genitalia.

  • Anal Paget disease is associated with anorectal adenocarcinoma.
  • It presents with a slowly-enlarging, unilateral, dry, scaly plaque.
Perianal extramammary Paget disease

Carcinoid syndrome

Carcinoid syndrome is the association of intestinal carcinoid with hepatic metastases.

  • Carcinoid syndrome causes flushing and diarrhoea.

Dermatomyositis

Dermatomyositis is classified as an autoimmune disease. In older adults with dermatomyositis, 15–50% have an underlying malignancy of the gastrointestinal tract, pancreas, lung, breast, or ovaries, or non-Hodgkin lymphoma.

  • Dermatomyositis associated with malignancy may precede the diagnosis of cancer by about six months.
  • Skin signs of paraneoplastic dermatomyositis include:
    • Heliotropic rash with periorbital oedema
    • Gottron papules on finger joints
    • Violaceous poikiloderma over the chest, upper back, elbows and knees
    • Nail signs: “ragged cuticle” and nail fold telangiectasias.
Dermatomyositis

Paraneoplastic pemphigus

Paraneoplastic pemphigus (PNP) is a rare acantholytic, mucocutaneous blistering disease.

  • PNP is rarely associated with tumours of the gastrointestinal tract.
  • Other associated cancers include non-Hodgkin lymphoma and other haematological diseases, thymoma, sarcoma, lung cancer, and melanoma.

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