Introduction
Bowel-associated dermatosis-arthritis syndrome (BADAS) is an uncommon neutrophilic
dermatosis characterized by arthralgias, fever, myalgias, and malaise as well as cutaneous
eruptions on the extremities and trunk. The characteristic skin lesions are erythematous
macules that evolve into purpuric papules, papulopustules, or tender subcutaneous
nodules within a few days.
1
First described as a consequence of bowel bypass surgery, BADAS has also been associated
with diverticulitis, inflammatory bowel disease (IBD), and peptic ulcers.
1
The pathophysiology of BADAS is thought to involve immune complex formation and deposition
in response to antigens from intestinal bacterial overgrowth. We present the first
reported case of BADAS in a patient with cystic fibrosis (CF).
Case report
A 47-year-old woman was admitted with diffuse joint pain, fever, night sweats, and
a papulopustular eruption involving the arms, upper back, and thighs (Fig 1). Her
medical history was significant for culture-negative endocarditis, periodic loose
stools, Clostridium difficile colitis, and CF (ΔF508 mutation). Laboratory results
on admission showed an elevated white blood cell count (23,300/μL), a normal platelet
count (426,000/μL), an elevated erythrocyte sedimentation rate (25 mm/h), a mildly
elevated C-reactive protein (5.3 mg/L), and a nonelevated rheumatoid factor (11 IU/mL).
Transthoracic echocardiography ruled out endocarditis. Blood cultures were negative,
but she was treated with empiric antibiotics (vancomycin, ceftolozane-tazobactam and
oxacillin).
Fig 1
BADAS lesions presented as diffuse papulopustular eruption of the (A) arms, (B) upper
back, and (C) thighs in a patient with CF.
Dermatology was consulted on the second day of hospitalization when the papulopustular
eruption had spread distally to involve the lower legs. A pustule was cultured and
three skin biopsy sections were obtained for histology, direct immunofluorescence,
and tissue culture. Bacterial culture from the pustule was negative. Tissue culture
and direct immunofluorescence (IgG, IgA, IgM, C3, fibrinogen) were also negative.
Histology revealed Sweet syndrome-like neutrophilic dermatosis in the dermis (Fig
2, A and B). Leukocytoclastic vasculitis was present (Fig 2, C). Dermal infiltrates
were composed of mixed neutrophils, lymphocytes, histiocytes, and few eosinophils
(Fig 2). The patient's clinical presentation and histologic findings were consistent
with BADAS. Within a few days of treatment with oxacillin (2 g/d) and ceftolozane-tazobactam
(4.5 g/d), the patient's arthralgias and skin lesions improved dramatically. The oxacillin
and ceftolozane-tazobactam were continued for an additional 2 weeks after discharge
from the hospital.
Fig 2
BADAS lesion characterized by neutrophilic dermatosis with mixed dermal infiltrates
composed of neutrophils, lymphocytes, histiocytes, and few eosinophils. Overt leukocytoclastic
vasculitis is present. (Hematoxylin-eosin stain; original magnifications: A, ×2; B,
×40, C, ×200.)
Discussion
BADAS presents episodically with a prodrome of influenza-like symptoms followed by
the development of skin lesions. The cutaneous manifestations initially appear as
asymptomatic, painful, or pruritic erythematous macules on the upper extremities and
trunk. Within a few days, these lesions transform into purpuric papules or papulopustules,
which may persist for up to 4 weeks.1, 2 Complications include diarrhea, liver dysfunction,
calcium oxalate renal calculi, hyperuricemia, mood changes, tenosynovitis, and vitamin
A or B1 deficiency.
1
In cases related to gastrointestinal (GI) surgery, symptoms may first appear 3 months
to 5 years after the procedure.
3
Histologically, BADAS shows superficial dermal edema and neutrophilic perivascular
invasion with leukocytoclasia.1, 2, 4 Vasculitis is often present in neutrophilic
dermatoses, occurring secondary to proteases or other noxious substances released
from neutrophils, not as a primary immune-mediated phenomena.
5
All of these histologic features were observed in our patient's skin lesions.
In 1979 Dicken and Seehafer
6
first proposed BADAS, formally known as bowel bypass syndrome, to describe 2 patients
who underwent end-to-side jejunocolic bypass or ileal bypass surgery.6, 7 The association
of BADAS with bypass procedures has since expanded to include other intestinal or
bariatric procedures and IBD.
2
The unifying feature in these conditions appears to be intestinal bacterial overgrowth
(eg, through the creation of blind loops of intestine). Intestinal bacterial overgrowth
and the subsequent increases in bacterial antigens (eg, bacterial peptidoglycans)
are hypothesized to induce an immune response that results in the formation of immune-antigen
complexes. These immune-antigen complexes deposit in the skin and joints resulting
in the cutaneous and arthritic manifestations of BADAS.
8
CF is an autosomal recessive disorder involving the CF transmembrane regulator (CFTR)
gene. The CFTR gene encodes the CF transmembrane chloride channel, which is widely
expressed in the skin, lungs, and GI tract. A high prevalence of small intestinal
bacterial overgrowth (SIBO) has been described in patients with CF.9, 10 The clinical
presentation in this case report (eg, history of periodic loose stools and CF) could
be explained by SIBO. The most common risk factors for the development of SIBO are
decreased gastric acid production and reductions in intestinal motility; patients
with CF are predisposed to both of these risk factors.
11
For example, patients with CF are more susceptible to gastroesophageal reflux and
are frequently prescribed protein pump inhibitors to reduce gastric acid production.
Moreover, CFTR receptor dysfunction in the GI tract results in thickened and acidified
intestinal secretions.
9
Thickened intestinal secretions reduce intestinal motility and predispose these patients
to intestinal obstruction.
9
Overall, these patients are more susceptible to SIBO; however, to our knowledge, BADAS
in a patient with CF has not been reported.
In this case report, we recount a patient with CF presenting with arthralgias, fever,
night sweats, loose stools, and a papulopustular eruption involving the upper back
and proximal extremities. The clinical signs and symptoms as well as the histopathology
were consistent with BADAS, presumably caused by SIBO. Alternate etiologies of BADAS,
such as GI surgery and IBD, were not present in this case. Until now, the relationship
between BADAS and CF was not reported. The incidence of BADAS among patients with
CF should be explored further to determine the extent of this relationship. Highlighting
the association between these entities will help practitioners recognize BADAS earlier
and avoid unnecessary diagnostic testing and treatments. Moreover, a better understanding
of the features that predispose individuals to BADAS may aid in the prevention and
treatment of this condition.