Blastomycosis Dermatitidis

Department Editor
Tania J. Phillips, MD, FRCPC

Overall Learning Objective: The physician or nurse participant will develop a rational approach to the evaluation and treatment of a variety of uncommon wounds and will have an increased awareness of the differential diagnosis of cutaneous wounds and the systemic diseases associated with these wounds.

Submissions: To submit a case for consideration in Diagnostic Dilemmas, e-mail or write to Managing Editor, WOUNDS, 83 General Warren Blvd., Suite 100, Malvern, PA 19355, mmcgovern@hmpcommunications.com.

Completion Time: The estimated time to completion for this activity is 1 hour.

Target Audience: This CME activity is intended for physicians and nurses who treat wounds.

At the conclusion of this activity, the participant should be able to:
1.    Identify etiologic agent of Blastomycosis and its various morphological forms
2.    Describe and recognize similar presentations of Blastomycosis with other systemic diseases
3.    Utilize appropriate treatment strategies for Blastomycosis.

Disclosure: All faculty participating in continuing medical education programs sponsored by The North American Center for Continuing Medical Education (NACCME) are expected to disclose to the activity audience any real or apparent conflict(s) of interest related to the content of their presentation. Dr. Cabigas, Dr. Niezgoda, and Ms. Verhage disclose that they have no financial conflicts relevant to the content of this activity.

Accreditation:
MD/DO: This activity is sponsored by the North American Center for Continuing Medical Education (NACCME). NACCME is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. NACCME designates this educational activity for a maximum of 1 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity. This activity has been planned and produced in accordance with the ACCME Essential Areas and Policies.

Nurses: ANCC: North American Center for Continuing Medical Education is an approved provider of continuing nursing education by the Pennsylvania State Nurses Association, an accredited approver by the American Nurses Credentialing Center’s Commission on Accreditation.  This continuing nursing education activity was approved by the PA State Nurses Association for 1 contact hour.  Provider #: 110-3-E-06. Provider approved by the California Board of Registered Nursing, Provider Number 13255 for 1 contact hour.

Conflict of Interest Resolution/Content Validation: In compliance with ACCME Standards for Commercial Support and NACCME’s policy and procedure for resolving conflicts of interest, this continuing medical education activity was reviewed by a member of the NACCME Wounds Advisory Board in January 2007 for clinical content validity to insure that the activity’s materials are fair, balanced, and free of bias toward the commercial supporter(s) of the activity; the activity materials represent a standard of practice within the profession in the United States; and any studies cited in the materials upon which recommendations are made are scientifically objective and conform to research principles generally accepted by the scientific community.

Method of Participation: Participants must read the article and take, submit, and pass the post-test by January 31, 2008. Participants must completely fill out the answer and evaluation form, answer at least 70% of the questions correctly, and mail or fax the answer/evaluation forms to:
Trish Levy, CME Director, NACCME
83 General Warren Blvd., Suite 100, Malvern, PA 19355
Fax 610-560-0501

This activity has been planned and produced in accordance with the ACCME Essential Areas and Policies.
Release date: January 31, 2007
Expiration date: January 31, 2008


Presentation

A 52-year-old man was referred by his primary care physician to the wound care clinic for evaluation and treatment of nonhealing wounds located on his left medial forearm and right lateral thigh. He presented with large, painless, foul smelling ulcerations, covered by slightly raised thick necrotic eschar. The lesions started as small, bluish blisters that slowly expanded outward in a radial fashion over the preceding 5 months. Initial measurements were 8 cm x 9 cm (forearm), and 13 cm x 16 cm (thigh). His wound care regimen at the time of consultation consisted of daily hydrogen peroxide irrigation.
This patient’s past medical history was essentially unremarkable. He did not have diabetes and had no chronic medical conditions. Social history was positive for a 40 pack/year smoking history and social alcohol consumption. Review of systems was negative for recent fever, chills, respiratory symptoms, cough or congestion, shortness of breath, and chest pain. He also denied abdominal pain and other gastrointestinal symptoms, anorexia, and weight loss.

Diagnosis

The patient was diagnosed with blastomycosis dermatitidis. Biopsy of wounds demonstrated pseudoepitheliomatous hyperplasia along with the identification of fungal spores consistent with Blastomyces. Fungal cultures also showed Blastomyces. Chest X-ray revealed a small nodule in the right middle lobe and some paratracheal adenopathy.

Discussion

Blastomycosis is an uncommon fungal infection that is endemic to southern central states in the US, especially those in the Mississippi River Valley. Accessibility to bodies of water, low pH, and high organic content are factors favorable to growth of the fungus and also explains why the great lakes area (especially Wisconsin) have reported the greatest incidence. Between 1986 and 1995, 670 cases of blastomycosis were reported to the Wisconsin Department of Health.¹ Of these cases, 635 were confirmed. Additional clinical data analyzed for 378 patients revealed that 76% had primary pulmonary disease with extrapulmonary manifestation, 18% had extrapulmonary disease without pulmonary symptoms, and 6% had both pulmonary and extrapulmonary signs.¹
Most cases of blastomycosis that present as skin lesions have no corresponding pulmonary or systemic manifestations. Although, disseminated blastomycosis has been known to either be transient and subclinical or severe and full-blown with pneumonic or pleuritic sequelae.² The causative agent, Blastomyces dermatitidis, is dimorphic occurring in conidial or spore form at room temperature and as the mycelial yeast form at normal internal body temperature (37˚C, 98.6˚F). This fungus is found in warm, moist, richly organic soil with decomposed vegetation, and wood. It is contracted via inhalation of the fungal component into the pulmonary system or via contaminated traumatic puncture directly into the dermis as can occur during gardening or with animal scratches. Animal blastomycosis can be seen in dogs, especially the hunting breeds that have their noses in contact with the soil. Upon inhalation, the spores are induced by the increased temperature and transformed into thick-walled budding yeast.
Once inhaled or deposited into tissue, the “seeded” fungus may be distributed hematogenously to other organs, such as the skin, bone, genitourinary tract, or central nervous system. Blastomycosis dermatitidis is also known as Gilchrist Disease, Chicago Disease, and North American Blastomycosis. It typically begins as a primary pulmonary infection but associated extrapulmonary involvement is often seen in most cases.³
Pulmonary infection presents with variable symptoms ranging from asymptomatic to fulminant respiratory distress syndrome. Symptomatic pulmonary infection typically initially manifests as dry cough, pleuritic pain, low-grade fever, and hoarseness. Associated complaints may include fever, malaise, fatigue, and weight loss.
If the pulmonary infection does not resolve spontaneously, progression of the disease can occur. An intact and fully functioning immune system is vital in preventing the growth and spread of blastomycosis. Immunocompromised individuals, such as those on chronic steroid therapy, organ transplant recipients, and patients with HIV, are at highest risk for infection.
Dissemination to the skin or other organs usually occurs early during the pulmonary phase but may be delayed and occur weeks to years after the primary exposure and initial pulmonary infection. Diagnosis, although illusive and challenging due to the vague symptomatology and variable trajectory of the disease process, can be made from 1) tissue biopsy stained with PAS or Gomori; 2) fungal culture which should be held for approximately 4 weeks and; 3) enzyme immunoassay tests. The most accurate method for diagnosing blastomycosis is with culture on Sabouraud’s agar, Mycosel agar, or brain-heart media. Visible colonies of white septated mycelium are present, which eventually turn into tan-colored colonies. Histological section demonstrates pseudoepitheliomatous hyperplasia, neutrophil-filled epidermal microabscesses and multinucleated giant cell infiltrates with the dermis where the fungal spores are located. Serologic tests lack sensitivity but enzyme immunoassays (ie, WI-1 antigen, a yeast cell wall protein) can aid in the diagnosis of blastomycosis.⁴
Initial skin lesions are typically characterized by a well-circumscribed ulcer surrounded by an inner margin of pustules and outer margin of papules. Transition to a crusted, draining, verrucous lesion with an irregular border and subcutaneous abscess formation is common. Dermal Blastomyces is often initially misdiagnosed as pyoderma gangrenosum, squamous cell carcinoma, and atypical vasculitis due to similar presentations. Blastomycosis should also be one of the differential diagnoses of lobar or segmental pneumonia, especially in patients who live in areas with high incidence of blastomycosis. Radiologic findings mimic those found in bronchogenic carcinoma, tuberculosis, histoplasmosis, silicosis, and sarcoidosis.⁵

Management

At the time of the initial wound care consult the entire eschar and devitalized tissue was sharply debrided. The underlying dermis revealed healing papillary dermal reticuli with early neoepithelialization noted in the center of the wound bed. The wound margins were hypertrophic and inflamed without frank induration. Punch biopsies were obtained due to the atypical appearance and suspicion of vasculitis. Tissue samples were sent for culture, gram stain, and pathological analysis. Histopathology reported reactive changes with acute and chronic inflammation, spongiosis, hyperkeratosis, and intraepithelial neutrophils. No evidence of fungal elements, vasculitis, cellular atypia, or neoplasm was reported.
Advanced wound care intervention was initiated and included a topical mixture of cadexomer iodine (Iodosorb®, Healthpoint, Forth Worth, Tex) and silver sulfadiazine (Thermazene®, Tyco Healthcare/Kendall, Mansfield, Mass). Cadexomer iodine (CI) dressings contain a 0.9% concentration of iodine, which is slowly released into the wound as the dressing absorbs the wound fluid. Apart from its antibacterial activity, CI provides an inflammatory stimulus in the wound via macrophage activation resulting in a cascade of inflammatory events leading to the influx of T-lymphocytes onto the wound area.⁶ Silver sulfadiazine (AgSD) and its antibacterial efficacy is attributable to only a small portion of the silver reacting with protein, chloride, and other components of body fluids, making the majority of it available for uptake by bacteria thus leading to their destruction. Silver sulfadiazine also has the inherent capability of facilitating keratinocyte replication and tissue epithelialization^7,8 while continuing to exert its efficacy in the ever-increasing issue of antibiotic-resistant organisms, such as Staphylococcus, Pseudomonas, and Candida.⁹ Thus, stimulation of the wound healing cascade by CI and AgSD’s ability of facilitating epithelialization seems to work synergistically. This combination has been proven to be clinically efficacious in the management of hundreds of patients in the authors’ practice.
The patient was seen for follow-up every other week. Examinations revealed an enlarging wound with reaccumulation of necrotic debris overlying an advancing indurated, inflamed, and ischemic outer ulcer margin. The prominent inflamed margins also contained crypts that had expressed purulent drainage with tissue compression. Interestingly, the center of the wound showed healing progression and epithelialization. Serial debridements were accomplished at regular intervals and included the use of ultrasonic assisted wound therapy.
Failure to control the advancing process with advanced wound care efforts resulted in surgical referral for operative and excisional debridement. Negative pressure wound therapy (V.A.C.® Therapy, KCI, San Antonio, Tex) was utilized postoperatively until the wound base showed compete granulation. The patient was then transitioned to topical papain-urea copper chlorophyllin complex (Panafil®, Healthpoint, Fort Worth, Tex).
Surgical specimens histopathology revealed pseudoepitheliomatous hyperplasia with marked acute, chronic, and granulomatous inflammation. Microabscesses were noted. Fungal spores were identified and were consistent with Blastomyces. The spores were moderately sized and demonstrated double contoured walls and broad base budding.
Due to the identification of Blastomyces, an infectious disease consult was obtained. Chest X-ray revealed a rounded opacity measuring 2 cm in the right middle lobe with retraction of the hila that was indicative of previous inflammatory disease sequelae. Itraconazole suspension (200 mg bid) was started. Antifungal treatment was continued for 6 months along with advanced wound care. Shortly after surgical excision of the lesions and initiation of systemic antifungal treatment, the wounds epithelialized and healed by secondary intent without further complications.

Conclusion

This case illustrates the challenge of diagnosis and management of cutaneous blastomycosis¹⁰ in a 52-year-old man with no pre-existing disease or other medical conditions. The patient lives with his 2 dogs in a semi-rural area of Wisconsin—part of the endemic region. He is an avid hunter and fisherman. These risk factors placed him in contact with the causative agent. His presentation and course of disease is consistent with information found in the literature. Blastomycosis is a diagnosis that requires a high index of suspicion due to the lack of definitive and serologic tests to confirm the disease, as well as the varied morphology in tissue.¹¹ Initial tissue biopsy is often nondiagnostic as demonstrated in this case. Due to the similarities to other systemic infections like tuberculosis or histoplasmosis, a misdiagnosis can contribute to disease progression, protracted course, and fatal outcome in immunocompromised patients. When properly recognized and diagnosed, itraconazole treatment for 2–6 months has been shown to yield favorable outcomes.^12,13