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Atypical histopathology in bowel-associated dermatosis-arthritis syndrome: A case report

  • Author(s): Patton, Timothy
  • Jukic, Drazen
  • Juhas, Elizabeth
  • et al.
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Atypical histopathology in bowel-associated dermatosis-arthritis syndrome: A case report
Timothy Patton DO1, Drazen Jukic MD PhD2, Elizabeth Juhas MD3
Dermatology Online Journal 15 (3): 3

1. Department of Dermatology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
2. Department of Dermatopathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
3. Department of Internal Medicine
University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. pattontj@upmc.edu


Abstract

Bowel-associated dermatosis-arthritis syndrome (BADAS) is characterized by a prodrome of fever, chills, and flu-like symptoms with subsequent skin eruptions, myalgias, and polyarthralgias. The syndrome was initially described following jejunoileal bypass surgery for weight loss. Histopathology of the skin lesions present in BADAS is described in the literature as identical to that of Sweet syndrome. We present a patient whose clinical history and physical exam were consistent with the diagnosis of BADAS. Dermatopathology in this case demonstrated a large subcorneal pustule without a significant dermal neutrophilic infiltrate. The histologic differential included subcorneal pustular dermatosis, bullous impetigo, or IgA pemphigus. The histology in BADAS may not necessarily be identical to Sweet syndrome, and the clinical picture alone plays an important role in diagnosis. The correct diagnosis of BADAS prevents a myriad of laboratory tests and allows for more effective symptom management in this chronic condition.



Introduction

Bowel-associated dermatosis-arthritis syndrome (BADAS) has been described in up to 20 percent of patients following jejunoileal bypass for morbid obesity in the 1960s, 1970s, and 1980s [1]. Though this procedure has largely been replaced with gastric bypass, the classic syndrome has not been eradicated. Originally entitled bowel bypass syndrome, it was first described by Ely in 1980 [1]. The condition has been reported in patients who have undergone small stomach and Roux-en-Y jejunectomy [2], ileoanal pouch anastomosis [3], jejunocolic bypass [4], ileocolic bypass [4], biliopancreatic diversion [5], Billroth II gastrectomy [6], and patients with gastric phytobezoar [7], diverticulitis with sigmoid stenosis [8], Crohn disease and ulcerative colitis [6]. Bowel-associated dermatosis-arthritis syndrome classically consists of a prodrome of fever, chills, and flu-like symptoms followed by myalgias, polyarthralgias, and characteristic inflammatory skin eruptions in the next 12 to 36 hours. Laboratory studies are typically within normal limits [1]. Onset of symptoms may be days to years following original gastrointestinal surgery, and the symptom complex may be self-limited or chronic and recurrent [1]. Current textbooks describe the histopathology of BADAS as identical to Sweet syndrome [9, 10]. We present a case of BADAS demonstrating histopathologic features of subcorneal pustular dermatosis.


Case Report

A 59-year-old woman presented to our office with complaints of a recurring rash of the last 15 years duration. She had undergone Roux-en-Y bypass surgery 17 years prior to presentation. She stated that 1 to 2 days prior to the onset of skin lesions, she would experience mild fevers and arthritis involving her metacarpophalangeal and proximal interphalangeal joints bilaterally. The skin lesions appeared as red papules and vesiculopustules with an erythematous halo, more concentrated on her arms and legs than on her trunk (Figs. 1 & 2). Multiple cultures of the lesions were negative. The lesions themselves were relatively asymptomatic causing only mild discomfort, although the appearance of the lesions was somewhat distressing to the patient. The arthralgias were becoming increasingly painful with each flare of her disease. Skin eruptions would resolve without sequelae in approximately 1 to 2 weeks. When the skin lesions were present, there were concerns from her supervisors at work that it was a transmissible disease, affecting her job as a nurse in the neonatal intensive care unit. She took no medications and her past medical history was significant for bowel bypass surgery which she underwent 17 years prior to her visit to our clinic.


Figure 1Figure 2
Figure 1. Vesiculopustules on the lower extremity
Figure 2. Close-up of skin lesions demonstrated in Fig. 1.

The patient's clinical history and physical exam were consistent with a diagnosis of BADAS, and punch biopsy of a small vesiculopustule on the lower extremity was performed. Histopathology demonstrated a large subcorneal pustule without a dermal infiltrate of neutrophils. Periodic acid-Schiff, periodic acid-Schiff digested, Fite, and acid fast bacilli stains failed to demonstrate any microorganisms (Figs. 3 & 4). The patient was treated with a short course of systemic corticosteroids with resolution of her skin lesions and systemic symptoms. She was placed on metronidazole 500 mg twice daily to prevent flares, but was lost to follow-up.


Figure 3Figure 4
Figure 3. Subcorneal pustule without significant dermal neutrophilic infiltrate (H&E x200)
Figure 4. View of subcorneal pustule (H&E x500)

Discussion


Neutrophilic dermatoses

Bowel-associated dermatosis-arthritis syndrome falls in the spectrum of non-infectious neutrophilic dermatoses which do not cause vessel wall destruction histopathologically. This category includes Sweet syndrome, pyoderma gangrenosum, Behçet's disease, rheumatoid neutrophilic dermatosis, familial Mediterranean fever, and neutrophilic eccrine hidradenitis [11]. Differentiation has traditionally been aided by the patterns of neutrophilic infiltrate in the dermatoses [8].


Clinical presentation

Skin lesions classically emerge as erythematous macules 3 to 10 millimeters in diameter and develop into papular, vesicular, and then pustular 2 to 4 millimeter lesions over the subsequent 1 to 2 days. The lesions are sterile and the eruption is usually concentrated on the upper extremities and torso, overall lasting 2 to 8 days with recurrence approximately every 1 to 6 weeks [1, 2, 6, 12]. Skin eruptions may exist in any stage from macule to pustule and may be pruritic, painful, or completely asymptomatic. Lesions may be difficult to distinguish from gonococcal sepsis both clinically and histologically [1, 11].

Arthralgias do not produce radiographic changes or deformities in BADAS. The polyarticular episodic joint pain lasts days to weeks and predominantly affects small peripheral joints such as the fingers and wrists. Polymyalgia with tenosynovitis has been reported [1].


Laboratory investigation

Laboratory evaluation of rheumatoid factor, anti-nuclear antibody, immunoglobulins, and uric acid are usually within normal limits [5]. Cryoglobulins in the serum have been noted in some patients during symptomatic periods [1, 6].


Dermatopathology

Histologically, BADAS has been described as identical to Sweet syndrome (acute febrile dermatosis) [1, 2, 4, 6, 11], a mature neutrophilic infiltrate in the dermis with papillary dermal edema [11]. BADAS characteristically does not result in vessel destruction. On biopsy, vessels are patent and there is no evidence for fibrinoid necrosis or infarction, and early reports suggesting such findings have been dismissed in later literature [1, 6, 13, 14]. This distinguishes BADAS from leukocytoclastic vasculitis. In addition, multiple staining techniques confirm the absence of microorganisms [1, 2, 6].

Several studies have suggested that the histopathology of cutaneous lesions is temporally dependent on disease progression [5, 7, 15]. Ely elaborated on the pattern of histologic changes seen in BADAS as the skin lesions progress from macule to pustule. The macular stage produces a perivascular mononuclear cell infiltrate; the papular stage produces edema of the papillary and reticular dermis. Neutrophils are concentrated in dermal venules in the former, and present diffusely in the dermis in the latter stage. In older papules and vesicles the neutrophilic infiltrate is more dense, incorporating nuclear debris and few eosinophils. Massive edema of the papillary dermis contributes to vesicle formation, while expulsion of neutrophilic debris through the epidermis results in pustules [1].


Pathogenesis

The pathogenesis of this syndrome is not well understood. It is theorized that overgrowth of bacteria in a blind loop or diseased bowel segment after surgery results in inflammation and the formation of an immune response to bacterial antigens [1]. Immune complexes may subsequently enter the circulation and deposit in target tissues [2, 5, 14]. It is proposed that this produces an inflammatory reaction in the skin and joints, resulting in the characteristic symptoms of BADAS [5, 6]. This is supported by the findings of abundant organisms in the blind bowel loop, cryoprecipitates of complement and antibodies to bacteria, immune complexes, response to antibiotics, and complete resolution following bypass reversal [2, 7, 12]. In some patients, skin-testing with Streptococcus pyogenes alone was able to reproduce or exacerbate the complete clinical picture of BADAS (flu-like prodrome, arthralgias, and skin lesions). Histopathology of the positive skin test sites was identical to naturally occurring skin lesions in the syndrome. Though group A streptococci have not been cultured from bypassed bowel, it has been suggested that the peptidoglycan antigen of these bacteria is common to many others and is responsible for the immunologic response [1].


Treatment

Tetracycline and metronidazole have been used to treat patients with BADAS with inconsistent results. In addition, non-steroidal anti-inflammatory drugs may alleviate arthralgias and daily prednisone can control symptoms. However, side effects of these therapies must be considered. Reversal of bypass is curative in the majority of patients who have undergone the procedure [4]. In patients without bowel bypass, treatment of underlying gastrointestinal disease has contributed to remission [6].


Conclusion

We present a case in which the histology of BADAS demonstrated a subcorneal pustule without a significant dermal neutrophilic infiltrate. The differential diagnosis suggested by the histopathology was subcorneal pustular dermatosis (Sneddon-Wilkinson disease), bullous impetigo, or IgA pemphigus. Subcorneal pustular dermatosis is a chronic relapsing eruption of sterile flaccid pustules on the trunk and proximal extremities favoring intertriginous zones. This disease is otherwise asymptomatic and has not been associated with the constitutional symptoms classically described in BADAS. Bullous impetigo primarily affects young children and consists of fluid-filled painless pruritic blisters from which Staphylococcus aureus can frequently be isolated. In IgA pemphigus, immunoglobulin A antibodies directed against desmosomal proteins in the epidermis create intraepidermal blistering. Systemic symptoms are uncommon. None of these entities were clinically consistent with our patient's presentation.

This case illustrates that BADAS has not disappeared or become obsolete with the discontinuation of widespread jejunoileal bypass surgery for morbid obesity, but perhaps has been ignored in the differential diagnosis of dermatologic and arthritic conditions in recent years. When considering that 10,000 to 20,000 bowel bypass surgeries were performed yearly in the 1970s and 1980s, and that 20 percent of patients experience dermatologic sequelae following this procedure, it is very likely that this syndrome is simply under-diagnosed today due to decreased awareness on the part of physicians [1, 5, 16].

The histology in BADAS may not necessarily be identical to Sweet syndrome. The complete clinical picture may be adequate to distinguish the two syndromes in cases in which the patient has a prominent history of gastrointestinal surgery or disease. Currently, Sweet syndrome is primarily a diagnosis of exclusion [11]. The correct diagnosis of BADAS prevents patients from becoming subject to a battery of unnecessary laboratory tests searching for an infectious etiology when skin and blood cultures are negative, and allows for more effective and rapid symptom management [2, 4, 5, 12]. Accurate diagnosis of patients affected with BADAS will undoubtedly draw attention to this overlooked syndrome in the medical community, and contribute to the alleviation of the chronic relapsing condition that can lead to frustration in undiagnosed patients.

References

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