Fox Den Disease: An Interesting Case Following Delayed Diagnosis

Pyoderma fistulans sinifica, also known as fox den disease, is a rare and poorly understood inflammatory disorder of the skin and subcutaneous tissues. This disorder is often mistaken for other inflammatory skin disorders and treated inappropriately. The authors describe the case of a 53-year-old male who presented to the colorectal surgery service with a longstanding diagnosis of perirectal Crohn’s disease. Despite aggressive immunosuppression and numerous surgical procedures, the patient continued to have unrelenting purulent drainage from the skin of his buttocks.   Following wide excision of the affected skin and subcutaneous tissues by the colorectal surgeon, the plastic surgery team reconstructed the 30 cm x 55 cm wound using a combination of local flaps and skin grafts. The initial pathology report of the excised specimen confirmed the presence of nonspecific abscesses and inflammation. Upon special request by the plastic surgery team, the sample was resectioned with the specific intent of establishing a diagnosis of fox den disease. The additional slides met the criteria for an unequivocal diagnosis of fox den disease. Immunosuppression was discontinued and the patient healed his wounds without complication. Fox den disease is often overlooked because of the obscurity of the disease and the special histological sectioning needed to establish a diagnosis. In this case, the patient was unnecessarily treated with immunosuppressive drugs for more than 3 decades because of a misdiagnosis. With increased awareness of fox den disease, perhaps its pathophysiology can be better elucidated as more patients are appropriately diagnosed and treated.

The authors describe the case of a 53-year-old male who presented to the colorectal surgery service of the Medical College of Wisconsin, Froedtert Hospital (Milwaukee, WI) with a long-standing diagnosis of severe perirectal Crohn’s disease. Symptoms began when the patient was approximately 17 years old when he experienced his first eruption of perirectal fistulas. The patient reported he had intense pain, swelling, and purulent drainage from the perirectal area. Since that time, he has undergone countless incision and drainage procedures of his perianal region, both at bedside and under general anesthesia. Additionally, the patient had been placed on various courses of immunosuppressive drugs including infliximab, methotrexate, steroids, and azathioprine. Despite these intense interventions by various specialists, the patient continued to experience frequent and recurrent perianal and buttock abscesses and fistulas. After speaking with the patient upon initial presentation to the author’s clinic, it was obvious the chronic odor, drainage, and pain had severely diminished the patient’s well-being and self-esteem. Specifically, he had pain with sitting and would avoid working and interacting with friends during flares of his disease. The patient’s inflamed buttocks with multiple draining sinus tracts is shown in Figure 1.

Although this patent carried the diagnosis of Crohn’s disease for more than 3 decades, he had never manifested the intestinal symptoms associated with inflammatory bowel disease. Additionally, during his hospital stay, and prior to a plastic surgery consultation, random biopsies of the patient’s gastrointestinal tract showed no evidence of disease. The diagnosis of inflammatory bowel disease had been called into question; however, no alternative definitive diagnosis had been hypothesized. At the time of the ablative treatment, the differential diagnosis had been expanded to include hidradenitis suppurativa and acne conglobata. The colorectal surgeon ultimately elected to perform a wide excision of the inflamed tissues, as the patient had failed to respond adequately to other avenues of treatment.

Following the radical excision of skin and subcutaneous tissue by the general surgery team, the patient was left with a skin defect on his buttocks and perineum (Figure 2) measuring 55 cm x 30 cm. He was treated with daily wet-to-dry dressing changes for 5 days prior to intervention by plastic surgery. Pathology results from the resected tissue were consistent with nonspecific abscesses and did not provide further information regarding the underlying source of the patient’s wounds.

During the reconstructive procedure, the patient was initially placed in the supine position, and split-thickness skin grafts were harvested from the anterior and lateral thighs, which appeared healthy and had no evidence of disease involvement. The patient was then moved to the prone position, and his wound was copiously cleansed with both pulse-lavage (Surgilav, Stryker, Kalamazoo, MI) and a hydrosurgery system (VersaJet, Smith & Nephew, London, England). A small area on the left lateral buttock retained some skin laxity and was closed primarily. The remainder of the wound was then covered with meshed skin graft, which was stapled into place. Additionally, a fibrin sealant (Tisseel, Baxter, Deerfield, IL) was sprayed over the graft and a bolster, fashioned from a sterile scrub sponge, was tied into the patient’s perineum to press the graft into the concavity. At the end of the case, a rectal tube was placed and the wounds were dressed with a protective membrane dressing (N-Terface, Winfield, Richardson, TX) and copious antibiotic ointment.

Postoperatively, the patient was instructed to lie in the prone position, but was allowed to ambulate for the first 3 weeks. Additionally, he was instructed properatively that he would not be able to sit for a full 6 weeks. Unfortunately, stool leakage from around the rectal tube necessitated frequent dressing changes with a nonadhering dressing.

During the patient’s hospital stay, the plastic surgery team sought assistance from the pathology department to better elucidate the cause of this patient’s inflamed and infected skin, as the initial specimens had been unable to help in establishing a unifying diagnosis. Tissue samples from the initial wide excision were resectioned with the intent of possibly establishing a diagnosis of fox den disease. Upon review of these newly sectioned samples, the senior pathologist determined that the histology was consistent with fox den disease, noting stratified squamous epithelial lined tracts and sinuses running in the subcutaneous tissue and parallel to the skin (Figure 3). Immunosuppressive medications were discontinued.

One month after the procedure, the patient was brought back to the operating room for staple removal and cauterization of hypergranulation tissue, as this proved too difficult and painful to perform with the patient awake. Photographic analysis of his wounds at that time revealed an estimated 88% take of the surface area initially grafted.

While there was complete loss of the skin graft in the perineum, this area of the patient’s wound ultimately healed by secondary intention.

The patient was compliant with positioning instructions and maintained good pressure relief over his graft sites. Despite some skin graft loss, all wounds epithelialized (Figure 4). Two years and three months after initial grafting, the patient reported he was free from all drainage and odor. He claims to have only minimal discomfort and has expressed a confident and optimistic outlook on his life. Although he does note some pressure in his ischial region, the patient has retained protective sensation and has not experienced skin breakdown over the bony prominences.

Fox den disease, also known as pyoderma fistulans sinifica, is a rare and poorly understood inflammatory disorder of the skin and subcutaneous tissues first described in 1962 by Krauspe and Stelzner.¹ Few reports have been written on the disease; the largest case series in the English language was from the authors’ institution (Medical College of Wisconsin, Milwaukee, WI) and published in the infectious disease literature.² At present, the underlying etiology of the disorder is not known and the only definitive treatment that remains is wide excision and subsequent reconstruction. Due to the obscurity of the disease, it is likely often overlooked and misdiagnosed as other chronic skin and soft tissue disorders such as hidradenitis, or in this case, perianal Crohn’s disease. Complicating the diagnosis is the fact that special histological sectioning is needed to definitively establish the pathology. The hallmark of fox den disease is the pattern of subcutaneous sinus tracts within the deep soft tissues running parallel to the fascia, resembling the architecture of a fox’s den.² These sinus tracts are lined with stratified squamous epithelium, and in contrast to hidradenitis, the adnexa of the skin are not involved.² These aforementioned characteristics are pathopneumonic for fox den disease.

Unfortunately, on routine sectioning, the tracts are often not adequately captured and, consequently, histology can only confirm the presence of subcutaneous inflammation. This had been the case with the patient described here, as previous biopsies of the involved tissue did not provide the necessary diagnostic criteria to confirm the diagnosis of fox den disease. It was only after the request had been made for further histological sectioning that the specific diagnosis could be confirmed.

Since the preponderance of the inflammation lies within the deep subcutaneous tissues, the term “pyoderma” is somewhat misleading, as it implies inflammation of the skin and dermis. The physicians at the authors’ institution prefer the term fox den disease as the inflamed fistulas and sinus tracts appear to originate from the subcutis and erupt through the skin.

The majority of reported cases involve the tissues in the perineum, buttocks, and genitalia; however, there are reports of the disease localized to the axilla.^3,4 In the case of this particular patient, establishing the diagnosis of fox den disease allowed his immunosuppression to be discontinued in good conscience, and he was thereby spared from the unwanted side effects of further dosing.

The authors of this report hope to raise awareness of this rare disorder by disseminating information about this case to others in the field. While many caregivers had been skeptical of this particular patient’s diagnosis of Crohn’s disease, no definitive alternative diagnosis was established by his prior physicians. Consequently, his excisional surgery was delayed and he was treated with various immunosuppressive regimens for more than 3 decades.

The authors hope that as more physicians develop a better understanding and awareness of this disease, perhaps more patients with fox den disease who are currently undiagnosed or misdiagnosed can be evaluated so as to better elucidate the underlying pathology of this rare disorder. A case of profound, longstanding, inflammation of the buttocks and/or perineum should prompt the astute physician to consider a diagnosis of fox den disease. With an expanded knowledge of fox den disease, perhaps patients with this disorder will be considered earlier for less aggressive but more effective treatment.

Ryan C. Stehr, MD; Nicholas Kim, MD; John A. LoGiudice, MD; and Kirk Ludwig, MD, FACS, FASCRS are from the Medical College of Wisconsin, Milwaukee, WI.

Address correspondence to:

John A. LoGiudice, MD
jlogiudi@mcw.edu

Disclosure: The authors disclose no financial or other conflicts of interest.