What is This Leg Growth With Necrotic Eschar?
Robert A. Norman, DO, MPH
Dr. Norman is in private practice in Tampa, FL. He is also associate professor, University of Central Florida School of Medicine, Orlando, and at Nova Southeastern School of Medicine, Davie, FL.
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A 58-year-old woman presented to the dermatology clinic because of an erythematous, tender, itchy, elevated lesion on her left knee. The lesion measured approximately
3.5 cm and had necrotic eschar. The patient reported having scratched her knee on a plant while gardening approximately 5 months earlier. She initially thought that the lesion was a blood blister, as it began to drain a blood-like substance, but did not emit any pus. She had continued to irritate the lesion by scratching it, and the lesion gradually doubled in size over the previous 4 months and became painful, which prompted her visit to the clinic.
A shave biopsy was done on the patient’s first visit. Her medical history included Crohn’s disease, hepatitis C, and chronic obstructive pulmonary disease, for which she had a double lung transplant in 2011. For her lung transplant, she was taking tacrolimus and valganciclovir. She was also taking prednisone and simvastatin.
Based on the case description and the photographs, what is your diagnosis?
A. Chromoblastomycosis D. Leishmaniasis
B. Tertiary syphilis E. Opportunistic bacterial infections
C. Leprosy
Answer and Discussion on next page
Diagnosis: Chromoblastomycosis (A)
Discussion
Chromoblastomycosis is a chronic, subcutaneous fungal infection, mainly affecting people who live in or have visited tropical and subtropical climates, yet it is occasionally seen in people living in temperate zones, such as Canada, the United States, and Europe.1 As it is widely considered an occupational hazard of farming in tropical rural regions, it has been suggested that men are more likely to be affected, as they are more commonly involved in agricultural labor than women, but no evidence-based relationship between sex and chromoblastomycosis has been established.1 The condition is often seen in patients between the ages of 30 and 50 years, possibly because it takes years for the disease to develop following traumatic inoculation of a dematiaceous fungi in the subcutaneous tissue, which generally occurs unbeknownst to the patient.1 The most common etiologic agents of chromoblastomycosis are Cladosporium carrionii, Fonsecaea compacta, Fonsecaea pedrosoi, Phialophora verrucosa, and Rhinocladiella aquaspersa.1,2
Chromoblastomycosis has been reported in a variety of immunocompromised persons, including individuals with diabetes,3 AIDS,4 and organ transplant recipients like the case patient.5 These patients are at particularly high risk of various infections, including from unusual pathogens, because of their weakened immune systems. In 2008, a group of physicians from India reported a rare case of chromoblastomycosis caused by a nonsporulating species of Rhytidhysteron in a 50-year-old kidney transplant recipient.5
Chromoblastomycosis most commonly presents as a papule or nodule that progresses into a verrucous or granulomatous plaque that expands over time. These lesions commonly occur on the hands, legs, and feet, particularly if they are not properly covered, while being exposed to these types of fungi while outside.2 The infection is usually localized; however, autoinoculation from scratching may cause the plaque to spread, giving it an annular appearance.
Pathology Findings of Chromoblastomycosis
The findings of the case patient’s skin biopsy were consistent with the diagnosis of chromoblastomycosis, showing sclerotic bodies that appear as round, thick-walled, brown bodies extracellularly and within the giant cells of the dermis. No special stains are needed to identify the fungi, which can be easily seen using hematoxylin and eosin staining.1 Typical histological findings include intraepidermal abscesses, granulomatous inflammation, and pseudoepitheliomatous hyperplasia.1
Treatment of Chromoblastomycosis
Death due to chromoblastomycosis is rare1; however, the treatment plan is limited, as this disease tends to be refractory to treatment. Immunocompromised individuals are at higher risk of morbidity and mortality from invasive fungal infections.6 There are three treatment modalities: physical treatment (eg, local thermotherapy, cryotherapy, electrosurgery, radiation), chemotherapy, and combination therapy, but the efficacy of treatment is often associated with the causative fungus, the clinical manifestation, and the severity of the lesions.7 Topical antifungal agents, such as itraconazole and terbinafine, are suggested for the long-term care of lesions.7 Amphotericin B injection is not recommended for the treatment of non–life-threatening fungal infections due to its serious side effects.8 Itraconazole has been recommended at oral doses between 200 mg and 400 mg daily.9 One study found pulse itraconazole to be more effective in treating chromoblastomycosis caused by Fonsecaea pedrosoi,9 showing that optimal treatment varies by case.
Our case patient requested surgical removal of her lesion after 2 months of treatment with itraconazole yielded little response. A wide margin excision was done to remove the lesion, and she was seen in follow-up 2 weeks later. Following the surgery, there was minimal scarring and the pain and irritation had resolved.
Ruling Out the Other Diagnoses
Some of the conditions included in the differential diagnosis of chromoblastomycosis are tertiary syphilis, leprosy, leishmaniasis, and opportunistic bacterial infections. A biopsy is required to make the diagnosis.
Tertiary syphilis. Tertiary syphilis is the result of untreated syphilis, which has progressed past the first and second stages. Tertiary syphilis is quite rare in modernized areas of the world because of antibiotics and the early recognition of its symptoms. The most common clinical feature of late syphilis are tumors of the skin, bones, or liver, also known as gummas, which present as
locally destructive skin lesions.10 Gummas appear as nodular lesions with an arciform pattern that can remain up to a few months. They can be mistaken for chromoblastomycosis, and a biopsy should be done to differentiate between them.
Leprosy. Leprosy, also called Hansen’s disease, is a chronic infection caused by the bacterium Mycobacterium leprae. It primarily affects superficial tissues, especially the skin and the peripheral nerves. Leprosy can cause erythematous papules, macules, nodules, and plaques on the skin, which are usually less pigmented than the surrounding normal skin.11 These lesions can be mistaken for chromoblastomycosis; however, lesions due to leprosy are often accompanied by sensory loss, with or without thickened nerves. Diagnosis of leprosy can be made via a biopsy, which would show Virchow cells.
Leishmaniasis. Leishmaniasis is a disease caused by protozoan parasites of the genus Leishmania. There are three forms of leishmaniasis: cutaneous, mucocutaneous, and visceral. Leishmaniasis is seen in patients who live in temperate and tropical climates throughout the world. Infection is transmitted by the bite of a sandfly; human transmission of the infection is extremely rare.12 Leishmaniasis cutaneous lesions usually begin as a well-demarcated, inflammatory papule that can grow to a nodule or plaque. It can later become ulcerated or verrucous in nature. The skin lesions typically resolve spontaneously with scarring. After an indeterminate amount of time, ranging from months to years, patients who have apparently healed from a cutaneous lesion can develop mucocutaneous lesions, which usually affect the nose and can result in destruction of vocal cords, nasal cartilage, and mucous membranes of the nose and mouth. Symptoms of visceral leishmaniasis can present like other infectious diseases, with patients presenting with wasting, massive splenomegaly, pancytopenia, hypergammaglobulinemia, and intermittent fevers.12 Biopsy of the lesions is required to make the diagnosis.
Opportunistic bacterial infections. Due to the appearance of necrotic eschar in the patient’s photographs as well as her exposure to the outdoors prior to presentation, it is possible to assume that the lesion was caused by pathogens typically transmitted by insect bites or other exposure to animals. Infection from Rickettsia, for example, commonly presents with eschars. Rickettsial pox presents with a red papule at the site of a mite bite, which can subsequently develop an eschar.13 At a tick bite site, an eschar caused by Rickettsial vasculitis may develop into a black spot on the skin. However, compared with the incubation period of chromoblastomycosis, the incubation period for rickettsial infections tends to be short at 1 to 2 weeks.
The author reports no relevant financial relationships.
References
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2. Bonifaz A, Carrasco-Gerard E, Saúl A. Chromoblastomycosis: clinical and mycologic experience of 51 cases. Mycoses. 2001;44(1-2):1-7.
3. Huang SS, Lee SC, Lee CW, Ho HC, Chang LC. Coexisting chromoblastomycosis and Mycobacterium fortuitum skin and subcutaneous infection. www.tsim.org.tw/journal/jour19-4/12.PDF. Published 2008. Accessed July 31, 2012.
4. Duggan JM, Wolf MD, Kauffman CA. Phialophora verrucosa infection in an AIDS patient. Mycoses. 1995;38(5-6):215-218.
5. Chowdhary A, Guarro J, Randhawa HS, et al. A rare case of chromoblastomycosis in a renal transplant recipient caused by a non-sporulating species of Rhytidhysteron. Med Mycol. 2008;46(2):163-166.
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8. PubMed Health. Amphotericin B injection. www.nlm.nih.gov/medlineplus/druginfo/meds/a682643.html. Accessed July 23, 2012.
9. Ungpakorn R, Reangchainam S. Pulse itraconazole 400 mg daily in the treatment of chromoblastomycosis. Clin Exp Dermatol. 2006;31(2):245-247.
10. PubMed Health. Syphilis. www.nlm.nih.gov/medlineplus/ency/article/000861.htm. Accessed July 23, 2012.
11. World Health Organization. Diagnosis of leprosy. World Health Organization Website. www.who.int/lep/diagnosis/en/index.html. Accessed July 23, 2012.
12. Weina PJ. Dermatologic manifestations of leishmaniasis. http://emedicine.medscape.com/article/1108860-overview#a0199. Accessed July 23, 2012.
13. Rathore MH. Rickettsial infection clinical presentation. http://emedicine.medscape.com/article/968385-clinical. Accessed July 23, 2012.