Dermatology

Lobomycosis (Lacazia loboi, Lobo's disease, Jorge Lobo's disease, keloidal blastomycosis, lacaziosis, leprosy of the Caiabi's)

Are You Confident of the Diagnosis?

Characteristic findings on physical examination

Lobomycosis is a chronic subcutaneous granulomatous disease. Lesions commonly occur in exposed areas: lower and upper limbs, outer ears, face and thorax. Patients often refer having suffered a previous traumatic event at the site of the lesion (animal or insect bites, splinter, ray sting). Lesions present initially as a single plaque, papule or nodule that eventually becomes multiple and disseminated. The most common presentation is the keloidal nodule, although verrucous, scar-like, sclerodermaform and ulcerated lesions have been described. Lesions are rarely monomorphic and usually present as a combination of the aforementioned. They can be hyperchromic, hypochromic or achromic and generally painless, but might be accompanied by dysesthesias.

Expected results of diagnostic studies

Histopathology is the gold standard for diagnosis. Uniform round to oval lemon-shaped cells measuring 6 to 12 micrometers in diameter disposed in chains with birefringent cell walls can be seen with hematoxylin & eosin (H&E) staining (Figure 1) or Gomori-Grocott (Figure 2) stained biopsy sections. Usually these organisms will be present in a diffuse background of non-necrotizing granulomas formed by a mixture of macrophages, lymphocytes and multinucleated giant cells.

Figure 1.

Chains of yeast cells in the dermis. Note the surrounding clear halos and refractile membrane.

Figure 2.

Gomori-Grocott stain highlighting the bridging connections between the cells.

Diagnosis confirmation

Differential diagnosis includes other infectious causes including cutaneous leishmaniasis (diffuse and borderline disseminated types), leprosy, sporotrichosis, paracoccidioidomycosis, cryptococcosis, chromoblastomycosis and blastomycosis, as well as other noninfectious clinical entities including dermatofibromas, dermatofibrosarcoma protuberans, keloids, and cutaneous malignancies such as squamous cell carcinoma, melanoma, Kaposi's sarcoma and appendageal tumors.

Who is at Risk for Developing this Disease?

Patients traveling to endemic areas with tropical and subtropical climates are particularly at risk. Human lobomycosis has been reported until now in nine South American countries (Brazil, Colombia, Surinam, Venezuela, Peru, French Guyana, Ecuador and Bolivia), three Central American countries (Costa Rica, Panama and Mexico) and more recently two cases have been reported in South Africa.

Age range of presentation is broad, ranging from 1 to 70 years. It occurs most commonly in males, although it is important to mention that gender is directly related to the occupational factor. Most cases have been reported in patients carrying out agricultural, fishing, hunting and mining activities.

Apart from humans, cases of lobomycosis have also been described in dolphins; although the possibility of humans acquiring the disease from dolphins appears low, there is one reported case of disease transmission from a dolphin to its attendant.

What is the Cause of the Disease?

Etiology

The causal agent of lobomycosis is the uncultivable dimorphic onygenales fungus Lacazia loboi.

Pathophysiology

Soil, vegetation and aquatic environments are believed to be the habitat of the fungus, which probably accesses the skin accidentally by penetration or accidental trauma. Once in the dermis, it is phagocytized, initiating a slow multiplication and insidious growth process. Hematogenous and lymphatic dissemination have been suggested as ways of extension, but they have not been confirmed. Direct contiguous extension is thought to be the main mechanism.

Systemic Implications and Complications

Only one case of visceral involvement has been reported to date in a patient with extensive disease of the lower limb who later developed a testicular lesion.

Secondary bacterial infections are common and are managed with topical and systemic antibiotics.

Malignancy, particularly squamous cell carcinoma, has been associated with chronic lesions, which tend to behave aggressively and recur after surgical excision. Suspicious areas arising in chronic lesional areas should be closely monitored.

Treatment Options

Table I. Therapeutic Options in Lobomycosis

Table I.

Therapeutic Options in Lobomycosis.
Surgical Options Excision with wide margins remains the optimal treatment
Medical Options Itraconazole (200 to 400mg/day) Clofazimine ( 100 to 200mg/day) with a 100mg/day maintenance dose for 2 years. Posaconazole: One case reported showed reduction of lesion after 75 weeks of treatment.
Physical Modalities Cryosurgery Electrocauterization

Optimal Therapeutic Approach for this Disease

Treatment options are summarized in the Table I. The best therapeutic option for small localized lesions is wide and deep surgical excision. Unfortunately, no satisfactory therapeutic modality currently exists, especially in large disseminated lesions.

Systemic antifungal therapy, including ketoconazole, fluconazole and amphotericin B have proven unsuccessful. Itraconazole, the most widely used azole for this disease, has revealed variable efficacy and to date, there have been no randomized, double blind, clinical studies supporting its complete efficacy. Therapeutic outcomes are mainly based on anecdotal case reports.

Clofazimine, a powerful antigranulomatous drug, has been found to be partially effective in controlling the progression of small lesions. Thus, the combination of clofazimine and itraconazole appears to be the best combination to date.

After achieving reduction of the lesions, surgery must follow in an attempt to alleviate the burden of fungal organisms and reduce the possibility of recurrence.

New extended spectrum triazoles such as voriconazole and posaconazole, which have proven to be effective in other subcutaneous mycoses, as well as refractory cases of eumycetomas and chromoblastomycosis, represent a promising therapeutic option for this disease.

Lobomycosis responds poorly to treatment and, despite aggressive chemotherapy, its course is often unremitting.

Patient Management

Combination therapy with clofazimine and itraconazole should be maintained until complete clinical resolution of the lesions is achieved.

Large lesions that undergo significant reduction should be surgically excised.

Serial biopsies at the periphery of regressed lesions are helpful to identify viable forms of the fungus and to assess transepidermal elimination of the microorganism.

Although rare, serious hepatotoxicity may occur with itraconazole. Liver function tests should be performed routinely during long periods of treatment.

Although infrequent, increased QTc/life-threatening arrhythmias may occur if used in association with other drugs such as quinidine. Careful EKG monitoring is mandatory.

Patients need to be advised that treatment periods are prolonged and that relapse is invariable in advanced stages despite intensive chemotherapy.

Unusual Clinical Scenarios to Consider in Patient Management

In patients with liver disease monitor closely liver function tests (LFTs) when using itraconazole. If hepatic condition worsens, discontinue treatment and follow up with serial LFTs.

Avoid using itraconazole in patients with severe heart failure. If congestive heart failure develops discontinue the drug.

Do not use itraconazole if the patient is taking quinidine or cisapride since its concomitant use with these drugs may precipitate the development of life-threatening arrhythmias.

In patients with liver or kidney function disorder monitor closely BUN / Cr and liver function tests if using clofazimine. If patient is receiving diuretics clofazimine dose must be carefully tailored to avoid hypokalemia. Eosinophilia is a frequent finding with no potential implications.

Before initiating or continuing any of these drugs always assess the risk/benefit.

What is the Evidence?

Lobo, JO. "Nova especies de blastomycose". Brasileira de Medicine. vol. 44. 1930. pp. 1227.

(First case described of lobomycosis by Jorge Lobo, a Brazilian dermatologist.)

Taborda, PR, Taborda, VA, McGinnis, MR. "Lacazia loboi General Nov, comb. Nov, the etiologic agent of lobomycosis". J Clin Microbiol. vol. 37. 1999. pp. 2031-33.

(Introduction of the genus Lacazia is proposed to accommodate Lacazia loboi, the obligate pathogen that causes lobomycosis in mammals)

Burns, RA, Roy, JS, Woods, C, Padhye, AA, Warnock, DW. "Report of the first human case of lobomycosis in the United States". J Clin Microbiol. vol. 38. 2000. pp. 1283-5.

(First case of human infection in Georgia, USA, of a 43-year-old white man.)

Torres, HA, Hachem, RY, Chemaly, RF, Kontoyiannis, DP, Raad, II. "Posaconazole: a broad spectrum triazole antifungal". Lancet Infect Dis. vol. 5. 2005. pp. 775-85.

(Posaconazole, a triazole drug that has a broad-spectrum use against most endemic and non-endemic fungi.)

Brito, AC, Tyring, SK, Lupi, O, Hengge, UR. "Lobomycosis". Tropical dermatology. Elsevier. 2006. pp. 207-9.

(Extensive review on lobomycosis, epidemiology, clinical presentation and treatment.)

Paniz-Mondolfi, AE, Reyer-Jaime, O, Davila-Jones, L. "Lobomycosis in Venezuela". Int J Dermatol. vol. 46. 2007. pp. 180-5.

(This extensive review covers the clinical-epidemiologic aspects and historical outlines of Lacazia lobia and presentation of two human cases.)

Fonseca, JJ. "Lobomycosis". Int J Surg Pathol. vol. 15. 2007. pp. 62-3.

(Short article with practical aspects of lobomycosis, as clinical presentation, epidemiology and treatment.)

Murdoch, ME, Reif, JS, Mazzoil, M, McCulloch, SD, Fair, PA, Bossart, GD. "Lobomycosis in bottle-nose dolphins (Tursiops truncatus) from the Indian River Lagoon. Florida: Estimation of prevalence, temporal trends, and spatial distribution". EcoHealth. vol. 5. 2008. pp. 289-97.

(Lobomycosis, a chronic fungal infection affecting humans and bottle-nose dolphins in Florida, USA.)

Talhari, C, Oliveira, CB, de Souza Santos, MN, Ferreira, LC, Talhari, S. "Disseminated lobomycosis". Int J Dermatol. vol. 47. 2008. pp. 582-3.

(Case report of an 86-year-old Brazilian woman with a long history of disseminated cutaneous lesions.)

Talhari, C, Chrusciak-Talhari, A, de Souza, JV, Araujo, JR, Talhari, S. "Exfoliative cytology as a rapid diagnostic tool for lobomycosis". Mycoses. vol. 52. 2009. pp. 187-9.

(Introduction of exfoliative cytology as a rapid diagnostic tool for lobomycosis as a simple, low cost and painless diagnostic method.)
You must be a registered member of Clinical Pain Advisor to post a comment.

Sign Up for Free e-Newsletters