Bowel-Associated Dermatosis and Arthritis Syndrome (BADAS) – A Literature Review With Diagnostic and Therapeutic Implications and a Report of Two Cases of BADAS Associated With Inflammatory Bowel Disease

Bowel-associated dermatosis-arthritis syndrome (BADAS) is a rare condition characterized by skin eruptions, fever, and arthritis. Initially, it was associated with post-bypass surgery and referred to as “bypass syndrome,” but later similar symptoms were reported in patients with other gastrointestinal (GI) diseases (Shagrin et al. 1971; Dicken 1986; Carubbi et al. 2013).

BADAS syndrome often occurs after bariatric surgery and co-occurs with inflammatory bowel disease (IBD) (Aromolo et al. 2023). The association of BADAS and IBD was first described by Jorizzo et al. (1983). Additionally, for the first time, a change in the nomenclature was proposed from “intestinal bypass syndrome” to “intestinal-related dermatosis and arthritis syndrome” (Jorizzo et al. 1983). IBD-related cases often present with significant GI symptoms, such as weight loss, abdominal pain, diarrhea, and hematochezia (Aromolo et al. 2023). The increasing awareness of IBD among doctors resulted in an increase in early diagnosis and, thus, a reduction in the occurrence of serious complications. However, the awareness of BADAS remains low, resulting in an underestimation of the morbidity rate and a lack of diagnostic and therapeutic recommendations.

We have selected and analyzed articles incorporating BADAS syndrome associated with IBD and confronted them with the two cases that occurred in our clinic.

The exact incidence of BADAS remains unknown. To our knowledge, only 21 cases of BADAS associated with IBD have been reported in the literature (Table 1). BADAS was observed with a predominant ratio of 15 (65%) women to 8 (35%) men. The average age at onset was 36.7 years, while the oldest patient was a 78-year-old male and the youngest a 4-year-old girl. Notably, a significant proportion of reported cases (4 cases, 17.4%) have occurred in pediatric patients. BADAS was associated with ulcerative colitis (UC) in 12 cases, Crohn’s disease (CD) in 10 cases and unspecified IBD in one case. In 12 cases, IBD was diagnosed before the occurrence of BADAS. In 10 cases BADAS was diagnosed simultaneously, thus, BADAS symptoms initiated the diagnostic process for IBD. Diseases that co-occurred with IBD in BADAS syndrome are presented in Table 1.

The precise pathogenesis of BADAS remains unknown. It has been postulated that BADAS is triggered by immune system activation due to intestinal surgery or IBD. IBD is associated with gut microbiota dysbiosis, characterized by increased Proteobacteria, Fusobacteria, and Bacteroides (Swidsinski et al. 2005; Aromolo et al. 2023). Post-GI surgery, patients often develop bacterial overgrowth (up to 10⁶ organisms/mL), with both aerobes and anaerobes present. The predominance of Bacteroides fragilis and Escherichia coli can be observed (Carubbi et al. 2013).

In addition to these alterations, IBD-associated dysbiosis is characterized by a reduction in overall bacterial diversity and a disproportionate expansion of specific facultative anaerobes within the phylum Proteobacteria, particularly the class Gammaproteobacteria, including adherent-invasive E. coli strains (Gevers et al. 2014). Moreover, increased relative abundances of Enterobacteriaceae and Fusobacterium nucleatum have been consistently reported in active disease states (Vich Vila et al. 2018; Yilmaz et al. 2019). Mucosa-associated microbiota studies have identified shifts at inflamed sites, with overrepresentation of Cloacibacterium spp. and members of the Tissierellaceae family, and depletion of commensal genera such as Neisseria (Hirano et al. 2018).

These microbial alterations are accompanied by functional changes, such as enhanced bile acid metabolism and altered amino acid pathways (e.g., tryptophan and taurine metabolism). Such changes can contribute to epithelial barrier dysfunction and further propagate inflammation. The proliferation of specific pathogens, such as certain strains of B. fragilis (e.g., enterotoxigenic B. fragilis) and F. nucleatum, along with an increase in mucolytic bacteria like Ruminococcus gnavus, further disrupts the microbial equilibrium and may promote mucosal injury and immune activation, which leads to translocation of the bacteria into the bloodstream (Carubbi et al. 2013; Czajkowski et al. 2023). Additionally, bacterial overgrowth can cause an accumulation of toxic bacterial metabolites, such as bacterial peptidoglycans, which may be involved in the initiation of a systemic immune response through the subsequent deposition of antigen complexes. It is strongly believed that the accumulation of the immune complexes in the skin and joints underlies the cutaneous and articular manifestations observed in BADAS (Carubbi et al. 2013; Linares et al. 2021; Aromolo et al. 2023; Czajkowski et al. 2023). Experimental validation of this theory has been conducted on animal models using bacterial peptidoglycans from group A streptococci, whose antigenicity and structure are similar to the human intestine, eliciting arthritis and cutaneous symptoms skin similar to those reported in BADAS (Ely 1980; Czajkowski et al. 2023).

Vitamin D deficiency, which is frequently reported in patients with GI disorders, has been identified as a potential risk factor for the development of BADAS. Although its role is not fully understood, vitamin D may reinforce mucosal barrier integrity by inhibiting intestinal apoptosis and regulating tight junction proteins (Gubatan and Moss 2018). It also demonstrates immunomodulatory effects, with receptors expressed on various immune cells, including T-helper 1 (Th1) and Th17 lymphocytes (Verway et al. 2010). A clearer understanding of the syndrome’s pathogenesis could contribute to the development of novel therapies and improved therapeutical outcomes.

BADAS encompasses both dermatological and rheumatological manifestations and, when occurring in association with IBD, may also involve GI symptoms (Table 2). The spectrum of skin lesions seen in the BADAS is very diverse and includes erythematous macules, plaques, nodules, vesicles with or without necrosis, as well as hemorrhagic vesicles and violaceous macules, occasionally associated with pruritus (Figures 1–3). The most common rheumatological symptoms of BADAS include fever, malaise, arthralgia, and peripheral arthritis (commonly limited to a few joints) (Figures 1–3).

Fig 1.

(A) Ankle swelling. (A, B) Erythematous macules and papules on the patient’s lower limbs.

Fig 2.

(A, B) Red spots and papules on the patient’s upper limbs. (C) After treatment, on 24-month follow-up.

Fig 3.

(A, B) Swelling and erythematous spots on the skin and asymmetric swelling of the ankle joints and wrist. (C, D) After treatment, the lesions on the upper and lower limbs healed.

The development of GI symptoms such as abdominal pain, weight loss, watery or bloody diarrhea, and other non-specific manifestations may indicate IBD exacerbation (Mendoza et al. 2003; Guerre-Schmidt et al. 2006; Barland et al. 2016; Oldfield et al. 2016).

In patients with BADAS, the most common abnormalities in laboratory tests are leukocytosis, anemia, elevated C-reactive protein (CRP), and accelerated erythrocyte sedimentation rate (ESR) (Table 1). D-dimer levels, previously not reported, were markedly elevated at 6478 ng/mL and 7200 ng/mL, being probably indicative of active systemic inflammation. Imaging tests can prove to be highly beneficial in the diagnosis of intestinal symptoms and most often show features of IBD exacerbation. The most common findings observed during endoscopy were signs of colitis, including ulcerations of the intestinal wall, along with associated mucosal swelling and redness, indicating active inflammation (Table 1). Histopathological examination of skin lesions also plays a key role in diagnosis processes.

The histopathology of the skin lesions is consistent with a neutrophilic dermatosis, often showing a leukocytoclastic vasculitis in the dermis. There are dense perivascular infiltrates of neutrophils and lymphocytes (Figure 4), accompanied by extravasation of erythrocytes, edema, elastosis, and fibrin deposition. Epidermal changes such as focal hyperkeratosis, parakeratosis, acanthosis, and flattening of the rete ridges can also be present (Figure 5).

Fig 4.

(A–D) The dermis shows intense perivascular, multicellular inflammatory infiltrates with a dominant neutrophilic component. Damaged blood vessels with fibrinoid necrosis are infiltrated by inflammatory cells. Dermis with elastosis and edema. Image provided by the Dermatology Clinic, PIM MSWIA.

Fig 5.

(A, B) Epidermal skin biopsy with focal hyperkeratosis and parakeratosis. Epidermal spinous layer with local acanthosis and flattening of the retinal ridges. Image provided by the Dermatology Clinic, PIM MSWIA.

The skin lesions in BADAS may resemble those seen in Sweet Syndrome, erythema nodosum, or pyoderma gangrenosum. However, the presence of additional symptoms, such as persistent fever, peripheral joint swelling, widespread joint pain, and weakness, alongside GI symptoms or a confirmed history of IBD, should raise suspicion of BADAS. Histopathological and imaging examinations play a key role in establishing an accurate diagnosis. However, to some extent, BADAS remains a diagnosis of exclusion, especially when it does not meet the diagnostic criteria of other diseases. Detailed analysis of differential diagnosis is presented in Table 3.

Bacterial translocation from the gut to the bloodstream appears to play a major role in the pathogenesis of BADAS (Carubbi et al. 2013; Aromolo et al. 2023; Czajkowski et al. 2023), supporting the grounded use of antibiotic therapy. Among the reported cases, metronidazole was the most frequently used antibiotic (five cases), while rifaximin, doxycycline, piperacillin–tazobactam, ciprofloxacin, and cefuroxime also showed effectiveness upon administration.

Anti-inflammatory medications are widely used in BADAS treatment. Prednisone was the most frequently administered, reported in 13 cases, while methylprednisolone (MP) was given as pulse therapy in five cases. Azathioprine was used in six cases, whereas cyclosporine and mycophenolate mofetil (MMF) were less common, reported in two, and one case, respectively.

Biological therapies were also documented. Infliximab (anti-TNF-α) was the most frequently employed, used in four cases. Other agents included ustekinumab (anti-IL-12/IL-23) in one case, vedolizumab (anti-α4β7 integrin) in one case, and canakinumab (anti-IL-1β) in one case.

Radical surgical interventions, such as proctocolectomy and subtotal or total colectomy, were performed in selected cases. Data on the effectiveness of these therapeutic options are summarized in Table 1.

The treatment of IBD-associated BADAS should be integrated with management of the underlying disease, and the choice of treatment should be tailored to the patient’s initial condition.

Given the significant role of bacterial overgrowth in the pathogenesis of BADAS, it is reasonable to consider antibiotic therapy against anaerobes (Jorizzo et al. 1983).

In our cases, positive outcomes were achieved with metronidazole or cefuroxime, administered either as monotherapy or in combination. The efficacy of cefuroxime may be due to its immunomodulatory properties, as it can modulate T-cell activity and downregulate proinflammatory T-cell phenotypes (Mor and Cohen 2013).

Furthermore, increased permeability of the inflammatory intestinal wall clearly plays a role in the pathogenesis of BADAS. Therefore, in cases related to IBD, it is essential to reduce inflammation in the intestines.

Anti-inflammatory therapy selection depends on the severity of the relapse. Systemic glucocorticosteroid therapy undoubtedly plays a principal role in inducing remission. Following remission induction, maintenance therapy should be carefully selected. In one of our cases, a young patient without comorbidities was treated with cyclosporine followed by azathioprine, a strategy previously reported in several cases, resulting in complete remission of BADAS symptoms. Biologic agents used for maintenance therapy (e.g., anti-TNF or anti-IL agents) appear to be equally effective in controlling BADAS, while having fewer side effects and contraindications than long-term corticosteroids or immunosuppressants. In the second case, in an elderly patient with numerous comorbidities, glucocorticosteroid therapy was discontinued due to contraindications (osteoarthritis, sigmoid diverticula (risk of perforation), chronic prostatitis, glaucoma, mental disorders) in favor of antibiotic therapy, and then infliximab therapy in doses of 5 mg/kg/every 2 months, resulting in improvement of intestinal symptoms and gradual disappearance of skin lesions and joint symptoms (and gradual healing of the fistula).

A similar approach was used in several cases, particularly when conventional treatment was contraindicated and a rapid, effective response was required (Table 1). These findings suggest that modern therapy offers a viable alternative to surgical treatment, which, although highly effective, can be significantly mutilating, particularly in children. In the presented pediatric cases, treatment with infliximab, vedolizumab, and canakinumab enabled avoidance of surgical intervention.

Based on the collected data, we propose a practical treatment algorithm, summarized in Table 4. In mild cases, a trial of antibiotics (e.g., metronidazole) combined with optimization of IBD therapy (e.g., 5-ASA) is recommended. For moderate to severe or refractory cases of BADAS, systemic glucocorticosteroids (e.g., prednisone 0.5–1 mg/kg/day) remain the first-line therapy and may be used in combination with other immunosuppressive agents such as cyclosporine or 5-ASA. In patients requiring a steroid-sparing strategy or for maintenance therapy, modern biologics are crucial for long-term disease control. When BADAS or other neutrophilic dermatosis occurs in the setting of active IBD and fails conventional therapy, anti-TNF inhibitor (particularly infliximab) should be considered a preferred option, given the best available evidence. Ustekinumab is an attractive option for patients who cannot receive or have failed anti-TNF therapy; evidence, while retrospective, shows promising results. Vedolizumab can be considered when intestinal activity is the main driver, although the evidence is sparce, and systemic biologics are generally more reliable for neutrophilic dermatoses. Consider IL-1 blockage (e.g. canakinumab) only in highly refractory, after careful risk assessment.

BADAS is a syndrome including dermatological, rheumatological, and gastroenterological symptoms, particularly related to IBD. The exact incidence of BADAS is still not fully known due to low disease awareness among specialists. The occurrence of both cases within a relatively short period at our institution suggests a significant underestimation of the prevalence of this syndrome. Available information on BADAS is limited to case reports, and there are still no clear diagnostic or therapeutic guidelines, which causes significant challenges for physicians. The exact pathogenesis of BADAS remains to be elucidated with further research. The exact pathogenesis of this syndrome still requires more in-depth research. However, available data indicate the important role of bacterial overgrowth and the impact of the movement of intestinal flora antigens, triggering a generalized inflammatory response. Furthermore, increased permeability of the inflamed intestinal wall contributes to the pathogenesis of BADAS. The manifestation of skin lesions during BADAS syndrome is very diverse: spots, papules, nodules, vesicles, and pustules, which to an inexperienced eye may resemble skin lesions such as: Sweet Syndrome or erythema nodosum, requiring completely separate treatment.

The presence of systemic symptoms such as persistent unexplained fever, peripheral joint swelling, diffuse arthralgias, and weakness – together with GI symptoms or a history of IBD – should raise suspicion for BADAS. Endoscopic evaluation may be helpful in the differential diagnosis, which in IBD-related cases most often indicates an exacerbation of IBD. Histopathological examination of skin lesions is of utmost importance: it typically reveals leukocytoclastic vasculitis with perivascular neutrophils and lymphocytes, along with dermal edema, erythrocyte extravasation, and fibrin deposition.

A recommended scheme of therapy is based on antibiotics, anti-inflammatory drugs, and biological treatment. Infliximab remains the best-supported biologic for neutrophilic dermatoses associated with IBD, including BADAS, and should be prioritized in severe or steroid-refractory cases with active intestinal disease. Ustekinumab represents an increasingly validated alternative with encouraging durability, particularly post-TNF inhibitors failure. Vedolizumab may be effective when skin disease tracks with gut activity but is less reliable for systemic neutrophilic inflammation, given its mechanism of action. Importantly, treatment of the underlying IBD should be initiated early, as appropriate treatment results in significant improvement in BADAS-related symptoms.

In our cases, BADAS treatment was focused on healing skin lesions and relieving GI symptoms. The first patient was treated with prednisone and cyclosporine to induce remission. Azathioprine was prescribed as a milder treatment option to maintain the effects. The second patient received metronidazole and ciprofloxacin, and biological therapy with infliximab was used to control the disease with good improvement.

Reduction of IBD flare-up clinically and on colonoscopy shows that control of digestive symptoms resulted in resolution of skin lesions and joint pain. These cases show that if the disease is properly treated, the symptoms of BADAS syndrome can disappear completely. Depending on the severity of symptoms, BADAS patients may be admitted to various departments; in the analyzed cases, these were the departments of rheumatology, dermatology, internal diseases, gastroenterology, and pediatrics. Due to the turbulent course of symptoms and the high risk of IBD and BADAS complications, a holistic approach to the patient is very important to make the correct diagnosis. For gastroenterologists, rheumatologists, and dermatologists, it is important to know about IBDs, their complications and comorbidities, as well as the possibility of quick diagnosis and implementation of appropriate treatment. This knowledge can prevent complications of the disease and avoid inappropriate treatment, which often includes radical surgery.

Further research is still greatly needed to expand our knowledge of BADAS, its epidemiology, symptoms, and possible comorbidities.