Inflammatory bowel disease (IBD) – including both Crohn's disease and ulcerative colitis – is a chronic, immune-mediated illness that doesn't just impact the gastrointestinal tract; extraintestinal complications are seen in as many as one in three affected patients [1]. Of these, skin symptoms are one of the most common, and can vary from lesions caused by the gut disease (for instance, when it is in remission, metastatic Crohn's disease causes skin lesions) to reactive disorders having similar immune mediated pathogenesis with the gut disease (for instance erythema nodosum and pyoderma gangrenosum).

The two most well characterized types of cutaneous manifestation of IBD are erythema nodosum and pyoderma gangrenosum, with erythema nodosum tending to follow the course of the intestinal disease, and pyoderma gangrenosum being more likely to have its own clinical trajectory [3]. Oral aphthous stomatitis, psoriasiform lesions and, less commonly, Sweet syndrome and perianal cutaneous fistulae have also been described with each having a unique implication for underlying disease phenotype and management [4].

The cutaneous morphology has been related already several times with the phenotype of Crohn's disease, its localisation in colon and an increased load of extraintestinal disease, pointing towards a shared immunopathogenic link between the two compartments and not only to a coincidental co-occurrence phenomenon [5,6]. An understanding of these associations is clinically useful because of the possibility of behaviour modifications and early detection of a cutaneous marker that may indicate a need for re-evaluating intestinal disease activity and increasing the treatment level.

Although there is ample international literature on the topic, local data on the frequency and pattern of the involvement of the skin in the course of IBD in Pakistan is still sparse. Thus, the aim of this study, was to find out what frequency and pattern of cutaneous manifestations arises among various patients with IBD referred to a tertiary care hospital in Pakistan for treatment and management and what are the clinico-pathological factors most strongly associated with it.

Study Design and Setting This was an observational study in three tertiary care hospitals of Pakistan in the Gastroenterology departments. The Data collection period ranged for six months from October 2025 to March 2026. Ethical Approval In all participating hospitals, ethics have been obtained before entering the study as per the principles laid out in Declaration of Helsinki. Written informed consent was acquired from all the patients involved. Sample Size and Sampling Technique A sample size of n = 220 was calculated with the formula for estimating a single population proportion, where p = 0.24, because of the reported prevalence of cutaneous manifestations in the group of patients with IBD in previous studies [1] and d = 0.06 (margin of error = 6%) and Z = 1.96 (95% confidence interval). This gave a minimum required sample size of 205 patient. To allow for accounts which might not be complete, a total of 220 patients were enrolled. A non-probability consecutive sampling technique was employed; in which all eligible patients presenting to the respective departments were sampled in a consecutive manner until the required number of patients were sampled. Inclusion Criteria ● Patients as adults, for whom a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) has been confirmed on endoscopic, radiological and histopathological grounds. ● Patients who were actively followed in the Gastroenterology department for at least 3 months before joining in the study. ● Patients who are willing to have a structured dermatological examination as part of the study assessment. Exclusion Criteria ● Patients with pending (indeterminate) colitis or other non-IBD chronic diarrhea indications ● History of preexisting, non-IBD dermatologic diseases which may affect skin assessment. ● Cases in which the clinical/endoscopic assessment records were not completed, and for which a calculated assessment score was unavailable. Data Collection A structured clinical evaluation, including type of disease and the disease activity, was done at the time of enrollment, while a standardized dermatological evaluation was performed at the time of the gastrointestinal consultation by the gastroenterologist in coordination with a dermatology consultant. Disease activity was categorised as 'disease active' or 'in remission' as per standard clinical, endoscopic and biochemical criteria. Diagnoses of the rash were made based on existing rubrics and categorized as erythema nodosum, pyoderma gangrenosum, aphthous stomatitis, psoriasiform lesions and other known dermatitis associated with IBD. Outcome Measures The main outcome was the prevalence of the entire spectrum of cutaneous reactions in registered patients with IBD. Secondary outcomes comprised the distribution of distinct manifestations types and correlation between the cutaneous manifestation and type of IBD diagnosis, duration of the disease, disease activity and presence of other extra-intestinal manifestations. Statistical Analysis The SPSS version 26.0 software was used to analyse data. The continuous variables were presented as mean ± SD and analyzed by independent samples t-test. Categorical variables were presented in the form of frequencies and percentages and compared using chi-square test. Statistically significant were set at a p-value < 0.05.

Accrued were 220 IBD patients during the six-month period, with 94 (42.7%) having Crohn's disease and 126 (57.3%) having ulcerative colitis. At the time of assessment disease was classified as active in 50.9%. Baseline characteristics are provided in Table 1.

An overall incidence of 24.5% was revealed, with cutaneous manifestation in 54 of 220 patients. As shown in Figure 1, of all affected patients, erythema nodosum was the most common finding, followed by aphthous stomatitis, pyoderma gangrenosum, psoriasiform lesions, and various dermatoses, but there were some differences in the specific type of manifestation between the Crohn's disease and ulcerative colitis subgroups.

Cutaneous manifestations were significantly more common in CD patients than in UC patients as shown in table 2 (63.0% versus 37.0% of affected patients, p < 0.001). Also, skin involvement was significantly associated with the presence of active disease at the time of evaluation (75.9% vs 42.8%, P<0.001), disease duration > 5 years (59.3% vs 37.3%, P=0.004), and coexistent non-cutaneous extraintestinal manifestations (e.g., peripheral arthritis, uveitis) (35.2% vs 16.9%, P=0.002). There was no significant difference in age between the two groups (patients with cutaneous manifestations vs. those without cutaneous manifestations) (34.6 ± 11.2 years vs. 37.8 ± 12.6 years, respectively, p = 0.089).

Table 1: Baseline Demographic and Clinical Characteristics (n = 220)

Table 2: Association Between Cutaneous Manifestations and Clinical Factors.

In this study, about one fourth of the patients with IBD reported cutaneous manifestation, a figure within the range of previous reports of 20 to 25 percent in large international cohorts – including the Swiss cohort of the IBD study [1]. The most commonly reported finding in this group was erythema nodosum, which, in accordance with the other review articles, is the most common finding associated with IBD [2,6]. Also, the difference in prevalence for skin lesions between Crohn's disease and ulcerative colitis was highly significant in this study, which is in line with a large body of previous evidence, including Farhi et al's large cohort study [3] that found a significant association with both Erythema nodosum and pyoderma gangrenosum in Crohn's disease patients. This trend may be explained by a similar underlying, more diffuse immune-mediated inflammatory reaction seen in Crohn's disease and is often transmural and manifests more variable extraintestinal manifestations [4]. The significant correlation between Active Intestinal Disease (AID) and skin lesions found here lends weight to the well-established notion that skin lesions in inflammatory bowel disease (IBD) are often related to the underlying natural course of the disease and that pyoderma gangrenosum may be less related to the course of the disease in the gastrointestinal (GI) tract [7]. The correlation with duration of disease is an additional argument to the fact that the sum of disease is responsible for long-term extraintestinal disease complications [9]. A local study in a tertiary care hospital in Karachi has reported a similar overall incidence of extra-intestinal manifestations in patients with IBD and was one of the most common groups of extra-intestinal manifestations, after articular manifestations [12]. Another study from a gastroenterology unit at Lahore also showed phenotype and active disease status as important risk factors for extraintestinal (including cutaneous) manifestations of CD, which is consistent with the associations found in this study [13]. The large skin response rate in patient subsets without specific skin involvement also helps to support a more systemic inflammatory process than one confined to the affected organ [8,11]. Knowing of this clustering is of real importance in terms of how it should influence the practice: When one EIM occurs, then the clinician should look for other EIMs, including dermatological evaluation, during comprehensive IBD care. In clinical practice, this study endorses the use of structured dermatological assessment as a tool to routinely integrate in the follow-up of any patient with IBD, specifically within Crohn's disease, who has longer disease duration or known extraintestinal involvement. As this cutaneous manifestation may be a marker for future intestinal disease flares, or it may occur concurrently, early detection would allow timely reassessment and/or changes in therapy, and with time should prevent the increase in disease burden both to the skin and the gut. A streamlined referral process between gastroenterology and dermatology with early identification and activation when a new skin lesion was observed or when the disease had been ongoing for more than 5 years, as identified in this study, could help institutionalize this practice without extent of additional resources at the tertiary care centers. Specific manifestation types of this cohort also have practical meanings for clinical vigilance, depending on the distribution of these manifestation types. Because erythema nodosum and aphthous stomatitis were the most prevalent findings and typically resolve when intestinal disease is well controlled, optimizing management of the intestinal disease may be enough in many affected patients. This is consistent with the findings of the largest cohort, the National Cooperative Crown's Disease Study, in which extraintestinal and perianal complications in IBD were systematically recorded [14]. In contrast, the smaller proportion of patients with pyoderma gangrenosum merits more close co-management with dermatology, as the pyoderma can deteriorate when luminal disease is not under control, and can lead to extensive tissue destruction if not timely recognised and treated [7]. These extra-intestinal manifestations, which include the skin, can also impact long-term outcome and overall management should be considered along with the luminal manifestations when making management decisions as described above [15]. Limitations: Since this is an observational, cross-sectional study, strong causal relationships have not been substantiated among the clinical factors found and the presence of skin findings. This study investigated the six-month period following study entry and the longitudinal relationship between skin lesion activity and the subsequent course of intestinal disease was not assessed. Larger, prospective, multi-center studies with longer follow-up are suggested to further elucidate this association, and to examine the consequences of targeted dermatologic screening on the broader IBD landscape.

About a quarter of patients with inflammatory bowel disease are affected by cutaneous manifestations, which are significantly related to the phenotype of Crohn's disease, intestinal disease activity, duration of disease, and occurrence of other extraintestinal manifestations. The most common findings in this group were erythema nodosum and aphthous stomatitis followed by psoriasiform lesions and pyoderma gangrenosum. The findings presented herein support the routine structured dermatologic screening of all patients with IBD, especially those at higher risk, for detection of cutaneous and systemic disease activity and for timely and comprehensive treatment in tertiary care centres in Pakistan.

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