Bowel-Associated Dermatosis-Arthritis Syndrome: A Case Report

Abstract

Introduction

Gastric bypass surgery is an effective surgical intervention for morbid obesity. However, it is not without risk. Gastric bypass surgery may produce malabsorptive or surgical complications, which can result in nutritional deficiencies as well as syndromes related to bacterial overgrowth in the blind loops of the bowel.

Case Presentation

Severe nutritional deficiencies may occur due to patient noncompliance with the prescribed regimen, or arise secondary to malabsorptive or mechanical surgical complications. We describe a case of a 37-year-old female who underwent gastric bypass surgery and experienced a recalcitrant eczematous eruption with sporadic subcutaneous, purulent nodules which completely resolved after the reversal of her bariatric procedure.

Conclusion

Since 2001, the number of morbidly obese patients who have undergone bariatric surgery has been increasing. As a result, clinicians can expect to more frequently encounter complications that can result from these procedures.

Introduction

Approximately 1 in 4 adults in the United States is obese.¹ Morbid obesity is defined as a Body Mass Index (BMI) of greater than or equal to 40 kg/m² or a BMI of greater than or equal to 35 kg/m² with high-risk comorbid conditions.¹ Bariatric surgery is the most effective weight-loss therapy for patients with morbid obesity. It can be considered when non-operative means, such as diet and exercise, nutritional counseling, and weight-loss programs have failed.¹ Bariatric surgery not only results in marked, sustained weight loss but also can contribute to the improvement or complete resolution of obesity comorbidities and improve the quality of life in these patients.¹ Types of operative procedures for sustained weight loss in morbid obesity include gastric bypass, vertical-banded gastroplasty, laparoscopic-adjustable gastric banding, biliopancreatic diversion, and duodenal switch.¹

Gastric bypass results in weight loss through 2 mechanisms: restriction of caloric intake with the creation of a small gastric pouch and selective malabsorption through reconstruction of the gastrointestinal tract, which allows food to bypass the distal stomach, duodenum, and proximal jejunum.¹ There are several gastric bypass procedures currently in use for weight loss, some of which may result in greater malabsorption and increased risk for adverse nutritional effects.¹

Gastric bypass surgery may produce malabsorptive or surgical complications, which can result in nutritional deficiencies¹ as well as syndromes related to bacterial overgrowth in the surgically-created blind loops of the bowel.^2–4

Malabsorption of specific micronutrients, as a consequence of surgically-altered gastrointestinal anatomy, produces predictable nutritional deficiencies managed by lifelong supplementation.⁵ Severe nutritional deficiencies may occur due to patient noncompliance with the prescribed follow-up regimen of nutritional supplements or arise secondary to malabsorptive or mechanical surgical complications.⁵

Since 2001, there has been a substantial increase in the number of morbidly obese patients who have undergone bariatric surgery.⁶ Consequently, clinicians can expect to more frequently encounter complications that result from these procedures. The following case report illustrates a patient who experienced several dermatological complications following bariatric surgery.

Case Presentation

A 37-year-old female presented with a pruritic rash lasting for 3 months. It was initially located on her inner thighs and spread to involve her feet, groin, abdomen, arms, and hands. She complained of intense vaginal itching as well. She had been treated unsuccessfully with multiple agents, including oral and topical antifungals, permethrin 5% cream, triamcinolone cream, and cetirizine, without improving her itching.

Her medical history was significant for type 1 diabetes mellitus, diabetic neuropathy, hypertension, hyperlipidemia, rheumatoid arthritis, depression, and hypothyroidism secondary to radioiodine (¹³¹I) ablation for Graves’ disease. Medications included insulin, gabapentin, venlafaxine, levothyroxine, enalapril, metoprolol, and fenofibrate. Methotrexate and etanercept prescribed for rheumatoid arthritis were discontinued 1 month before admission.

She had a history of gastric bypass surgery for obesity 6 months before the onset of the symptoms. She had been recently hospitalized for nausea, vomiting, abdominal pain, and altered mental status. An endoscopy and a computed tomography scan of the abdomen and pelvis were unremarkable. A transjugular liver biopsy revealed nonalcoholic steatohepatitis. During her hospitalization, she was treated for tinea corporis, protein malabsorption, elevated ammonium levels, bacteremia, and urinary tract infection. She was then transferred to a rehabilitation facility.

Examination revealed eczematous plaques on her hands, feet, and ankles, with confluent erythema on the lower legs that partially blanched. There was a disruption of surgical scars with cutaneous hemorrhages noted. Perianal and perivaginal bright red erythema was observed (Figures 1 and 2). Erythema and edema of the tongue, and fissures of the oral commissure with erythema were noted as well (Figure 3). There was diffuse thinning of scalp hair and a complete loss of the pubic, axillary, arm, and leg hair (Figure 4). Bilateral pitting edema extended proximally to her knees.

Figure 1.

Eczematous erythematous excoriated plaques appear on the bilateral buttocks with a bright red perianal erythema. bedside ultrasound of the pelvis, transverse plane, showed free fluid in the pelvis.

Figure 2.

Bright red atrophic-appearing plaques are seen on the bilateral labia majora, extending to the mons pubis.

Figure 3.

Erythema and edema are shown on the tongue, with fissuring of the oral commissure.

Figure 4.

A complete loss of hair is shown in the left axilla.

Lab evaluation showed a serum albumin of 1.5 g/dL (3.4–4.8 g/dL). Biopsies of 2 eczematous lesions showed mild psoriasiform acanthosis of the epidermis with slight spongiosis, overlying stratum corneum with parakeratosis, focal dyskeratosis, and occasional neutrophils. There was a slight pallor of the upper epidermis. In the dermis, a predominantly lymphocytic perivascular infiltrate, with a few neutrophils and eosinophils, was present. The periodic acid-Schiff (PAS) stain was negative. The findings were consistent with a nutritional deficiency.

Topical clobetasol was given for symptomatic relief of itching. She was started on crushed B vitamins, zinc, and vitamin C. Nutritional support was started for severe protein malnutrition consistent with Kwashiorkor. Improvement of the glossitis, angular cheilitis, and rashes was noted with no new petechial lesion. Despite aggressive oral supplementation, hypoalbuminemia worsened, so the patient was transferred to another facility for intravenous (IV) alimentation.

Nine months later, we were again consulted on this patient for a skin eruption at another rehabilitation facility. She was admitted from a different hospital to continue IV vancomycin treatment for skin abscesses. The patient complained that her skin itched and burned and was “coming off in big chunks.” She noted that her skin eruptions had completely resolved when she was on total parenteral nutrition but that they returned 3 months prior to admission. She also complained of photophobia for 3–4 weeks. Her scalp hair was thinning, and she lost all her body hair from the neck down. Her fingernails stopped growing, and she always felt cold. She was weak, and her bones ached all the time, but the pain was different than what she experienced with her rheumatoid arthritis and diabetic neuropathy. Her stools were loose, and she was still losing weight despite eating 100% of her meals and consuming frequent snacks. She now weighed 127 pounds, down from a pre-surgical weight of 303 pounds, for a cumulative weight loss of 176 pounds over 19 months.

Additionally, she had a recent onset of painful skin abscesses that were being treated with incision and drainage, IV vancomycin, and topical mupirocin. A culture of the fluid from the lesions grew methicillin-resistant Staphylococcus aureus. After incision and drainage, the lesions were noted to heal poorly and were more painful. She complained of a new painful nodule on her scalp that began 5 days prior. She noted that it appeared similar to her previous lesions that had been treated with incision and drainage (Figure 5).

Figure 5.

An erythematous nodule was found on the occipital scalp. This nodule was biopsied with results consistent with bowel-associated dermatosis-arthritis syndrome.

Current medications included hydrocodone with acetaminophen, iron sulfate, cyanocobalamin, folate, mupirocin topical, and IV vancomycin in addition to insulin, gabapentin, venlafaxine, and levothyroxine.

Examination revealed eczematous plaques with sharply defined borders on the upper and lower extremities, including the palms, soles, trunk, and groin. Conjunctivitis and glossitis were noted, along with peri-anogenital erythema. An exquisitely tender erythematous nodule with a central pustule and crust was seen on the left occipital scalp. A punch biopsy of this pustular lesion and a shave biopsy taken from an eczematous plaque on the left dorsal hand were sent for histopathological examination.

Laboratory testing showed a normal serum vitamin B₁₂ level. The patient’s plasma zinc level, drawn 7 days after initiation of oral zinc sulfate supplementation of 220 mg 3 times a day, was low at 49 μg/dL (60–130 μg/dL), consistent with zinc deficiency.

Histopathologic examination of the shave biopsy taken from a plaque on the left dorsal hand showed psoriasiform hyperplasia of the epidermis with a pallor of the upper portion of the epidermis with a few neutrophils. These changes were similar to those seen previously and were consistent with a nutritional disorder. Histopathologic examination of the scalp nodule showed psoriasiform hyperplasia with a focal area of ulceration and a diffuse infiltrate of neutrophils throughout the dermis (Figures 6 and 7). PAS, Fite, and Brown-Brenn stains were negative.

Figure 6.

The histopathology of bowel-associated dermatosis-arthritis syndrome (10x magnification) is shown as taken from a punch scalp biopsy, which revealed a diffuse infiltrate of neutrophils throughout the dermis and psoriasiform hyperplasia.

Figure 7.

The histopathology of bowel-associated dermatosis-arthritis syndrome (20x magnification) is shown in a scalp punch biopsy, which revealed a diffuse infiltrate of neutrophils.

The histopathology of bowel-associated dermatosis-arthritis syndrome (BADAS), formerly known as bowel-bypass syndrome, consists of a diffuse infiltrate of mature polymorphonuclear lymphocytes.⁷ Therefore, histopathology can be consistent with BADAS.⁷ Our patient’s clinical presentation, low plasma zinc level, histopathology, and resolution of skin eruption with replacement were consistent with a diagnosis of acquired zinc deficiency and acrodermatitis.

She was treated with zinc, broad-spectrum antibiotics, and colchicine. Although the skin manifestations improved, the patient continued to lose weight despite adequate dietary caloric and protein intake. Her bypass procedure was finally reversed 1 year after she initially presented, and the patient’s skin eruptions completely resolved.

Surgical reconstruction of the normal intestinal anatomy and anti-inflammatory and anti-neutrophilic agents, such as prednisone, have improved other patients’ symptoms in similar cases.⁸ She was seen 6 months later for a follow-up evaluation and had no active eczematous plaques or subcutaneous nodules. She stated that her skin cleared shortly after her reversal procedure. Her weight gradually increased after her reversal. She was seen again 1 year later with a weight of 188 lbs. After 3 years of follow-up, she has had no additional episodes of neutrophilic dermatosis.

Discussion

Although there are reports in the literature of multiple nutritional deficiencies related to gastric bypass procedures, we believe this is the first case report of a concomitant acrodermatitis-like eruption due to an acquired zinc deficiency and skin findings related to BADAS. Clinicians caring for patients with intestinal bypass should consider that skin eruptions may be associated with several different mechanisms, as was the case in our patient.

Zinc plays a critical role in the function of hundreds of zinc-dependent enzymatic pathways that regulate protein, lipid, and nucleic acid synthesis and degradation.⁹ Zinc is absorbed in the duodenum and proximal jejunum. Patients who undergo bariatric surgery, especially surgeries that bypass these areas of the small intestine, have decreased absorptive capacity.¹⁰ For this reason, the American Society of Metabolic and Bariatric Surgery recommends zinc supplementation for all post-weight loss surgery patients.¹¹ Zinc deficiency can result in many biological and clinical consequences. Patients with zinc deficiency may develop erythematous plaques and desquamation in the perioral and perineal areas and extremities.⁹ Other findings may include diarrhea, stomatitis, angular cheilitis, blepharitis, conjunctivitis, photophobia, onychodystrophy, delayed wound healing, suboptimal immune function, and depression or apathy.⁹ Our patient had many of the signs and symptoms of zinc deficiency.

Histopathological findings of skin biopsies in zinc deficiency vary with the age of the lesion. A psoriasiform epidermal hyperplasia with confluent parakeratosis along with pallor of the superficial third of the epidermis, with or without necrosis, may be seen.¹²

Zinc deficiency may be treated with zinc sulfate or zinc gluconate.⁹ Replacement needs vary, and oral dosing may need to be titrated to overcome gastrointestinal losses due to malabsorption. Our patient responded well to zinc replacement with the eventual complete resolution of her symptoms.

Bowel-associated dermatosis-arthritis syndrome is a recurrent, episodic illness consisting of characteristic skin lesions, arthralgia, myalgia, and constitutional symptoms, such as fever, chills, and malaise.^2–4,13,14 It was first reported in the early 1970s and was seen in up to 20% of patients surgically treated with jejunoileal bypass surgery for morbid obesity.² The proposed mechanism of this entity involves the deposition into target tissues of circulating immune complexes that form against bacterial antigens from overgrown bacteria in a blind loop of the bowel.² It has since been reported in gastric bypass surgery, inflammatory bowel disease, and other intestinal bypass procedures. It can occur from 1 to 6 years after the responsible bowel surgery, although there has been a case of BADAS occurring 10 years after gastrointestinal surgery.^3,14 Our patient developed lesions and myalgia approximately 18 months after the gastric bypass.

Patients with bowel-related diseases who have not undergone gastric bypass surgeries are rarely reported to develop BADAS. Four cases in 1983 demonstrated patients with identical symptoms, with a history of gastric disease and no history of gastric bypass surgery.¹⁵

Characteristic cutaneous lesions are erythematous macules that progress to papules, plaques, and vesicopustules within 48 hours, last from 2 to 8 days, and may recur in intervals of 4 to 6 weeks.^2,13 They may be painful, pruritic, or asymptomatic. What is characteristic of these skin eruptions is that they heal without scarring.¹⁶ These lesions tend to favor the proximal extremities and trunk.³ Tender erythematous subcutaneous nodules may also be seen, and when on the legs, may clinically resemble erythema nodosum.² It has been reported that BADAS has a varied clinical presentation. Out of 31 cases, 10 presented with vesiculopustular dermatosis, 6 had transient erythematous nodular plaques, 4 had transient urticarial lesions, and 2 had spontaneous ecchymosis.¹⁷ The clinical morphology and distribution of our patient’s lesions and time to recurrence are consistent with that seen in this syndrome.

Histologically, a dense diffuse dermal infiltrate of predominantly neutrophils can be seen without infective organisms. Similar patterns are seen in Sweet’s syndrome, Behçet’s disease, and the early phase of pyoderma gangrenosum.^3,13 The patient’s biopsy showed a similar pattern, and special stains for organisms using PAS, Fite, and Brown-Brenn stains were negative.

Antibiotics such as tetracycline, doxycycline, minocycline, clindamycin, and metronidazole reduce bacterial overgrowth in the bowel, which may improve symptoms.³ Systemic prednisone or neutrophilic inhibiting drugs such as colchicine, dapsone, and thalidomide may also be helpful. It has been shown that surgical debridement of necrotic tissues does not improve this condition.¹⁸ For patients with inflammatory bowel disease, treatment should be directed at controlling the underlying bowel pathology. Only surgical revision or resection of the affected bowel is curative in patients who have undergone bowel bypass.⁸

Conclusion

The number of bariatric surgeries has increased significantly over the past 2 decades. Clinicians need to be aware of the signs and symptoms of nutritional deficiencies and other complications that can arise from alterations in the gastrointestinal anatomy. With a limited number of cases, BADAS is a clinically important syndrome to recognize. These patients easily remain undiagnosed and can be subjected to repeated non-therapeutic incision and drainage procedures.

Funding Statement

This research was supported (in whole or in part) by HCA Healthcare and/or an HCA Healthcare-affiliated entity.