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Cutaneous leishmaniasis in soldiers returning from deployment to Iraq
Cutaneous leishmaniasis in soldiers returning from deployment to Iraq LTC James F. Pehoushek, MC, USA, MAJ David M. Quinn, MC, USA, and MAJ William P. Crum, MC, USA Fort Sill, Oklahoma Cutaneous leishmaniasis is becoming a frequently encountered problem in soldiers returning from deployments to areas in Southwest Asia. Two cases of cutaneous leishmaniasis diagnosed at a military treatment facility in soldiers returning from Iraq are presented. Diagnostic considerations and procedures are reviewed as are the histopathologic findings and treatment options. ( J Am Acad Dermatol 2004;51:S197-200.)
CASE REPORTS Case 1 A 24-year-old white male active duty Army enlisted soldier was referred to our clinic for multiple nonhealing lesions of the hands, upper extremities, abdomen, neck, and face. He noted only mild pruritus of the affected areas and denied any pain of the lesions. He was otherwise in good health and was currently on hydroxychloroquine for malarial prophylaxis. He was not receiving any treatment for his skin lesions. The patient noted that the lesions had developed approximately 6 months into his recent deployment to Southwest Asia. His recent travel history included 1 month in Kuwait and 8 months in Iraq. He recalled being bitten frequently by small flies. On examination, the patient was noted to have approximately 10 lesions distributed over the back surfaces of the hands bilaterally (Fig 1), abdominal wall, chest, nuchal area, and left preauricular area. The lesions were all erythematous papules and plaques with superficial scale. Many of the more developed lesions had central nodules with eroded or ulcerated centers. A 6-mm punch biopsy was performed on the abdominal lesion. Case 2 A 33-year-old white male active duty Army officer was referred to the dermatology clinic with a 3The pagination of this article was incorrect as originally published (2004:51;S125-S128). Please use the corrected page numbers listed online at www.eblue.org, in the corrected table of contents, or in the December 2004 index in future citations. This supplement is made possible through the generous support of Stiefel Laboratories for the American Academy of Dermatology. From the Departments of Dermatology, Pathology, and Primary Care, Reynolds Army Community Hospital, Fort Sill, Oklahoma. Funding sources: None. Conflicts of interest: None identified. Reprint requests: Allergy and Dermatology Specialists, Inc, 6320A West Union Hills Dr, Suite 100, Glendale, AZ 85308. James F. Pehoushek, MD, E-mail: [email protected]. doi:10.1016/j.jaad.2004.06.018
month history of a nonhealing lesion on his right fourth toe. He had originally been seen by a primary care physician who had diagnosed the condition as a bacterial abscess with secondary cellulitis. He had been treated with oral Augmentin and cephalexin, which had resolved the apparent cellulitis, but not improved the toe lesion. He was also being treated with becaplermin gel (Regranex) and immobilization without any improvement of the lesion. The patient was otherwise in good health and denied any other medical problems or history. He noted that he had developed the lesion on his foot approximately 2 weeks after returning from deployment to the Persian Gulf region. His recent travel history included 1 month in Kuwait and 2 months traveling between Iran and Iraq. He recalled being bitten numerous times by small flying insects. On physical examination, the patient was noted to have an ulcerated erythematous plaque on the dorsal aspect of the right fourth toe (Fig 2). Further examination revealed a second nontender, 20- 3 15-mm scaly erythematous plaque with a moist central erosion of the left popliteal area (Fig 3). There was no lymphadenopathy and no mucosal lesions were noted. Two 6-mm punch biopsies were performed of the lesion of the left popliteal area. Portions of both patients’ biopsy specimens were submitted to both our hospital’s laboratory and to the Walter Reed Army Institute of Research (WRAIR) in Silver Spring, Md, for analysis. Our facility evaluated cytologic touch preparations made from the biopsy specimens with Diff-Quik. Hematoxylin and eosin (H&E)-prepared permanent sections were also evaluated. Specimens were submitted to WRAIR for polymerase chain reaction (PCR), culture, H&E, and cytologic evaluation. Cytologic evaluation of the touch preparations for both cases showed multiple 2- to 4-m organisms within tissue macrophages (Fig 4). The organisms had both a nucleus and a visible kinetoplast, consistent with the amastigote stage of Leishmania. S197
S198 Pehoushek, Quinn, and Crum
Fig 1. Case 1. Close-up image of initial lesions on back of right hand with central domed, eroded, and crusted erythematous nodules.
H&E-prepared slides were also diagnostic for leishmaniasis. Biopsy specimens showed a diffuse dermal infiltrate composed of lymphocytes, plasma cells, and histiocytes. Numerous histiocytes were filled with micro-organisms with identifiable kinetoplasts consistent with leishmaniasis. WRAIR corroborated the diagnosis of leishmaniasis. The causative organism in the two cases was identified as L major by culture and PCR. Both patients were transferred to the infectious disease department at Walter Reed Army Medical Center (WRAMC) in Washington, DC, for treatment. After completion of treatment, the patients were seen in follow-up at our facility and had significant resolution of all lesions.
DISCUSSION Current US military efforts have placed a large number of US military personnel in areas of the world in which leishmaniasis is endemic. With recent shifts to a larger reserve component in our military personnel, a significant number of those serving in the Southwest Asian theaters will be returning to civilian lives soon after returning from their military duties. As can be appreciated from the two cases presented above, leishmaniasis is a disease that may not be apparent until some time after an individual returns home. Leishmaniasis is also a condition that can be easily mistaken for a variety of other conditions that present with similar appearing lesions. Leishmaniasis, which is nearly exclusively transmitted by sandfly bites, has been of significance to military personnel throughout history. More than 10,000 cases of leishmaniasis were documented in World War I and 1500 cases during World War II. During the Gulf War approximately 440 cases of
J AM ACAD DERMATOL NOVEMBER 2004
Fig 2. Case 2. Initial erythematous ulcerated plaque on right fourth toe.
leishmaniasis were diagnosed.1 The World Health Organization (WHO) estimates that 1.5 million cases of cutaneous leishmaniasis occur annually worldwide.2 Of all cases of cutaneous leishmaniasis, 90% occur in Afghanistan, Brazil, Peru, Saudi Arabia, and Syria.3 In a report on soldiers returning from Operation Desert Storm covering 1990 to 1991, 12 cases of viscerotropic leishmaniasis and 20 cases of cutaneous leishmaniasis were diagnosed.4 A recent Morbidity and Mortality Weekly Report documenting 22 cases of cutaneous leishmaniasis in US military personnel diagnosed between May 2002 and August of 2003 noted that the majority (82%) were infected while in Iraq and another 9% each in Kuwait and Afghanistan.5 The median deployment duration was 60 days before the appearance of the initial lesions. The median number of lesions at the time of the initial evaluation was 3 (range: 1-9). None of the patients experienced systemic symptoms. Of these cases, 74% had positive cultures and, of these, all grew out L major. All patients were treated with sodium stibogluconate. Military vector surveillance for infected sandflies revealed an overall infection rate of 1.4% in Iraq (as high as 2.3% in Tikrit, Iraq).5 As noted above, military personnel returning from Afghanistan are also at risk for leishmaniasis. The prevalence of cutaneous leishmaniasis caused by infection with L tropica is approximately 2.7% in Kabul, Afghanistan, with the WHO estimating 200,000 active cases of the disease.6 A recent briefing to military providers noted that, as of mid-February 2004, more than 300 cases of cutaneous leishmaniasis have already been diagnosed from the current military operations in Iraq. It is estimated that up to 10% of the military personnel who are serving in the
J AM ACAD DERMATOL VOLUME 51, NUMBER 5
Fig 3. Case 2. Ulcerated scaly erythematous plaque of left popliteal area.
Persian Gulf area may be infected with leishmaniasis.7 In recently reported cases, the distribution of lesions was more common on exposed areas of the skin. Lesions were most frequently noted on the upper and lower extremities followed by the trunk, back, and face. The initial lesions are at the site of sandfly bites. The incubation period can be from weeks to months after the initial infection. Clinically, the lesions begin as a nontender, nonpruritic, erythematous papules. They may be wet or dry and become fibrotic or hyperkeratotic with healing. In addition, there may be eczematous, psoriasiform, varicelliform, or verrucous qualities noted. Gradually, lesions tend to widen in size and develop serous crusting and ulceration. Granuloma formation typically ensues giving the lesion raised borders and an erythematous ridge, which is referred to as the ‘‘volcano sign.’’ The surrounding area may exhibit lymphangitic spread with palpable cords and subcutaneous nodules. Secondary bacterial infection may complicate the picture. There are usually no associated systemic symptoms.1,3,8 After infection, adequate immunologic response eliminates the parasite and species-specific immunity results. This immunity has not been shown to be absolute and reinfection is possible. There is limited cross-reactivity in some cases.1 The extent and presentation of disease depend on several factors, including the humoral and cell-mediated immune response of the host, the virulence or the infecting species, and the parasite burden.8 In the cases we have seen at our facility, the initial diagnosis could be made on the cytologic touch preparation alone. Confirmation was made by H&E and PCR. Speciation was possible by culture or PCR. Several other cases were ruled out after evaluation at WRAIR. None of the latter cases showed evidence of leishmaniasis on cytology or H&E initially at our facility. Recent guidance from WRAIR and the
Pehoushek, Quinn, and Crum S199
Fig 4. Tissue macrophages with multiple intracellular organisms. Note that each organism contains nucleus and smaller kinetoplast. (Touch preparation stained with Diff Quik; original magnification: 3600.)
Armed Forces Institute of Pathology (AFIP) has recommended that a scraping be performed at the base of the ulcer of the lesion with a No. 15 blade. A thin layer of the material obtained from this scraping is then evenly smeared on glass slides for Diff-Quik staining and the slide is then interpreted locally. For any nondiagnostic cases, the stained slides and a portion of ethanol-preserved scraping material are to be submitted to the AFIP for review and PCR analysis. Based on the experience at our facility, it is also advisable to obtain tissue in the form of a 4-mm punch biopsy specimen for routine H&E pathologic evaluation to rule out conditions other than leishmaniasis. A single punch biopsy specimen can easily be used to obtain enough material for touch preparation, H&E, and PCR. With the appropriate staining solutions, a preliminary diagnosis can be made in a matter of minutes in much the same way as a potassium hydroxide or Tzanck preparation. (For more information on Leishmania testing, contact the CDC’s Division of Parasitic Diseases at (770) 488-4475.) Although the diagnosis of leishmaniasis must be considered for patients with the appropriate history, experience has shown that other diagnostic considerations should be kept in mind. The differential diagnoses of cutaneous leishmaniasis include cutaneous malignancies, other infectious causes, and a variety of inflammatory dermatoses reactions.1,8 The decision to treat leishmaniasis is based on various factors. Old World cutaneous leishmaniasis tends to resolve spontaneously and the indications for treatment include lesions that are disfiguring, painful, infected, over joints, or slow to heal.1,8 Several therapies are currently available in the United States.9 Pentavalent antimony treatment is available in the form of sodium stibogluconate
S200 Pehoushek, Quinn, and Crum
(Pentostam). WRAMC and Brook Army Medical Center in San Antonio, Tex, are currently providing treatment to all military personnel with sodium stibogluconate under an ongoing treatment protocol. It is also available from the Centers for Disease Control and Prevention as an investigational drug.8 The experience with sodium stibogluconate from WRAMC has shown the most common side effects to be chemical pancreatitis, myalgia, rash, and elevated transaminases.10 Meglumine antimonate (Glucantime) is another pentavalent antimony therapy option that is currently licensed for use in France. Other therapy options for cutaneous leishmaniasis include Dapsone and ketoconazole. Topical paromomycin is showing promise for cutaneous disease from L mexicana but is not available in the United States at this time. There are currently no Food and Drug Administration (FDA)-approved vaccines or prophylactic medications available.8 Additional therapies that have shown potential efficacy for treating cutaneous leishmaniasis are cryotherapy and thermosurgery. In a study conducted in Amman, Jordan, liquid nitrogen was applied to active lesions with a cotton swab for 15 to 20 seconds with a 1-minute thaw and repeated once. A series of up to 3 treatments was given at 3-week intervals. Of 215 patients seen in follow-up, all but one was noted to have significant clinical response.11 In another study, 201 patients were treated with a localized current field-radio frequency device to deliver a single treatment of a 30-second application of 508C heat to active lesions. At 8 weeks follow-up of 191 patients, total cure was noted in 90% of the patients (L mexicana was noted to be the most common causative organism for the disease in this area).12 Thermosurgery is FDA approved for the treatment of cutaneous leishmaniasis. The US Army is acquiring the equipment to provide thermosurgery therapy. Although most physicians, and particularly dermatologists, are aware of leishmaniasis, it is not a common diagnosis in most practices in the United States. As military personnel strengths increasingly rely on reserve soldiers for missions abroad, the occurrence of diseases acquired during military operations will become more commonplace in the civilian medical practice. As a result, civilian medical providers will need to expand their ability to identify,
J AM ACAD DERMATOL NOVEMBER 2004
diagnose, and treat conditions such as leishmaniasis and others, which typically are limited to other areas of the globe. The cases presented in this article emphasize the importance in obtaining an appropriately detailed history and physical examination. It is clear that as our world becomes ‘‘smaller,’’ our differential diagnoses must become more expansive. REFERENCES 1. Keeling JH. Tropical parasitic infections. In: James WD, editor. Textbook of military medicine. Part III, disease and the environment, military dermatology. Washington (DC): Office of The Surgeon General at TMM Publications Borden Institute Walter Reed Army Medical Center; 2003. p. 256-63. 2. Centers for Disease Control and Prevention—Division of Parasitic Diseases. Fact sheet—Leishmania infection (leishmaniasis). Available from:URL:http://www.cdc.gov/ncidod/dpd/ parasites/leishmania/factsht_leishmania.htm. Accessed January 11, 2004. 3. World Health Organization information fact sheet. The leishmaniases and Leishmania/HIV co-infections. Available from: URL:http://www.who.int/inf-fs/en/fact116.html. Accessed January 11, 2004. 4. Centers for Disease Control and Prevention. Viscerotropic leishmaniasis in persons returning from Operation Desert Storm—1990-1991. MMWR Morb Mortal Wkly Rep 1992;41: 131-4. 5. Centers for Disease Control and Prevention. Cutaneous leishmaniasis in US military personnel—Southwest/Central Asia, 2002e2003. MMWR Morb Mortal Wkly Rep 2003;52: 1009-12. 6. Reithinger R, Mohsen M, Aadil K, Sidiqi M, Erasmus P, Coleman PG. Anthroponotic cutaneous leishmaniasis, Kabul, Afghanistan. Emerg Infect Dis 2003;9:727-9. 7. Dooley DP. Great planes regional medical command leishmaniasis briefing. Brook Army Medical Center, Fort Sam Houston, Texas. February 18, 2004. 8. Stark CG, Wortmann G. Leishmaniasis. eMedicine.com. Available from: URL: http://www.emedicine.com/med/topic1275.htm. Accessed December 18, 2003. 9. Abramowicz M, editor. Drugs for parasitic infections. The medical letter on drugs and therapeutics. Available from: URL: http://www.medletter.com. Accessed April 12, 2002. 10. Wortmann G, Miller RS, Oster C, Jackson J, Aronson N. A randomized, double-blind study of the efficacy of a 10- or 20-day course of sodium stibogluconate for treatment of cutaneous leishmaniasis in United States military personnel. Clin Infect Dis 2002;35:261-7. 11. al-Majali O, Routh HB, Abuloham O, Bhowmik KR, Muhsen M, Hebeheba H. A 2-year study of liquid nitrogen therapy in cutaneous leishmaniasis. Int J Dermatol 1997;36:460-2. 12. Velasco-Castrejon O, Walton BC, Rivas-Sanchez B, Garcia MF, Lazaro GJ, Hobart A, et al. Treatment of cutaneous leishmaniasis with localized current field (radio frequency) in Tabasco, Mexico. Am J Trop Med Hyg 1997;57:309-12.
CASE REPORTS Case 1 A 24-year-old white male active duty Army enlisted soldier was referred to our clinic for multiple nonhealing lesions of the hands, upper extremities, abdomen, neck, and face. He noted only mild pruritus of the affected areas and denied any pain of the lesions. He was otherwise in good health and was currently on hydroxychloroquine for malarial prophylaxis. He was not receiving any treatment for his skin lesions. The patient noted that the lesions had developed approximately 6 months into his recent deployment to Southwest Asia. His recent travel history included 1 month in Kuwait and 8 months in Iraq. He recalled being bitten frequently by small flies. On examination, the patient was noted to have approximately 10 lesions distributed over the back surfaces of the hands bilaterally (Fig 1), abdominal wall, chest, nuchal area, and left preauricular area. The lesions were all erythematous papules and plaques with superficial scale. Many of the more developed lesions had central nodules with eroded or ulcerated centers. A 6-mm punch biopsy was performed on the abdominal lesion. Case 2 A 33-year-old white male active duty Army officer was referred to the dermatology clinic with a 3The pagination of this article was incorrect as originally published (2004:51;S125-S128). Please use the corrected page numbers listed online at www.eblue.org, in the corrected table of contents, or in the December 2004 index in future citations. This supplement is made possible through the generous support of Stiefel Laboratories for the American Academy of Dermatology. From the Departments of Dermatology, Pathology, and Primary Care, Reynolds Army Community Hospital, Fort Sill, Oklahoma. Funding sources: None. Conflicts of interest: None identified. Reprint requests: Allergy and Dermatology Specialists, Inc, 6320A West Union Hills Dr, Suite 100, Glendale, AZ 85308. James F. Pehoushek, MD, E-mail: [email protected]. doi:10.1016/j.jaad.2004.06.018
month history of a nonhealing lesion on his right fourth toe. He had originally been seen by a primary care physician who had diagnosed the condition as a bacterial abscess with secondary cellulitis. He had been treated with oral Augmentin and cephalexin, which had resolved the apparent cellulitis, but not improved the toe lesion. He was also being treated with becaplermin gel (Regranex) and immobilization without any improvement of the lesion. The patient was otherwise in good health and denied any other medical problems or history. He noted that he had developed the lesion on his foot approximately 2 weeks after returning from deployment to the Persian Gulf region. His recent travel history included 1 month in Kuwait and 2 months traveling between Iran and Iraq. He recalled being bitten numerous times by small flying insects. On physical examination, the patient was noted to have an ulcerated erythematous plaque on the dorsal aspect of the right fourth toe (Fig 2). Further examination revealed a second nontender, 20- 3 15-mm scaly erythematous plaque with a moist central erosion of the left popliteal area (Fig 3). There was no lymphadenopathy and no mucosal lesions were noted. Two 6-mm punch biopsies were performed of the lesion of the left popliteal area. Portions of both patients’ biopsy specimens were submitted to both our hospital’s laboratory and to the Walter Reed Army Institute of Research (WRAIR) in Silver Spring, Md, for analysis. Our facility evaluated cytologic touch preparations made from the biopsy specimens with Diff-Quik. Hematoxylin and eosin (H&E)-prepared permanent sections were also evaluated. Specimens were submitted to WRAIR for polymerase chain reaction (PCR), culture, H&E, and cytologic evaluation. Cytologic evaluation of the touch preparations for both cases showed multiple 2- to 4-m organisms within tissue macrophages (Fig 4). The organisms had both a nucleus and a visible kinetoplast, consistent with the amastigote stage of Leishmania. S197
S198 Pehoushek, Quinn, and Crum
Fig 1. Case 1. Close-up image of initial lesions on back of right hand with central domed, eroded, and crusted erythematous nodules.
H&E-prepared slides were also diagnostic for leishmaniasis. Biopsy specimens showed a diffuse dermal infiltrate composed of lymphocytes, plasma cells, and histiocytes. Numerous histiocytes were filled with micro-organisms with identifiable kinetoplasts consistent with leishmaniasis. WRAIR corroborated the diagnosis of leishmaniasis. The causative organism in the two cases was identified as L major by culture and PCR. Both patients were transferred to the infectious disease department at Walter Reed Army Medical Center (WRAMC) in Washington, DC, for treatment. After completion of treatment, the patients were seen in follow-up at our facility and had significant resolution of all lesions.
DISCUSSION Current US military efforts have placed a large number of US military personnel in areas of the world in which leishmaniasis is endemic. With recent shifts to a larger reserve component in our military personnel, a significant number of those serving in the Southwest Asian theaters will be returning to civilian lives soon after returning from their military duties. As can be appreciated from the two cases presented above, leishmaniasis is a disease that may not be apparent until some time after an individual returns home. Leishmaniasis is also a condition that can be easily mistaken for a variety of other conditions that present with similar appearing lesions. Leishmaniasis, which is nearly exclusively transmitted by sandfly bites, has been of significance to military personnel throughout history. More than 10,000 cases of leishmaniasis were documented in World War I and 1500 cases during World War II. During the Gulf War approximately 440 cases of
J AM ACAD DERMATOL NOVEMBER 2004
Fig 2. Case 2. Initial erythematous ulcerated plaque on right fourth toe.
leishmaniasis were diagnosed.1 The World Health Organization (WHO) estimates that 1.5 million cases of cutaneous leishmaniasis occur annually worldwide.2 Of all cases of cutaneous leishmaniasis, 90% occur in Afghanistan, Brazil, Peru, Saudi Arabia, and Syria.3 In a report on soldiers returning from Operation Desert Storm covering 1990 to 1991, 12 cases of viscerotropic leishmaniasis and 20 cases of cutaneous leishmaniasis were diagnosed.4 A recent Morbidity and Mortality Weekly Report documenting 22 cases of cutaneous leishmaniasis in US military personnel diagnosed between May 2002 and August of 2003 noted that the majority (82%) were infected while in Iraq and another 9% each in Kuwait and Afghanistan.5 The median deployment duration was 60 days before the appearance of the initial lesions. The median number of lesions at the time of the initial evaluation was 3 (range: 1-9). None of the patients experienced systemic symptoms. Of these cases, 74% had positive cultures and, of these, all grew out L major. All patients were treated with sodium stibogluconate. Military vector surveillance for infected sandflies revealed an overall infection rate of 1.4% in Iraq (as high as 2.3% in Tikrit, Iraq).5 As noted above, military personnel returning from Afghanistan are also at risk for leishmaniasis. The prevalence of cutaneous leishmaniasis caused by infection with L tropica is approximately 2.7% in Kabul, Afghanistan, with the WHO estimating 200,000 active cases of the disease.6 A recent briefing to military providers noted that, as of mid-February 2004, more than 300 cases of cutaneous leishmaniasis have already been diagnosed from the current military operations in Iraq. It is estimated that up to 10% of the military personnel who are serving in the
J AM ACAD DERMATOL VOLUME 51, NUMBER 5
Fig 3. Case 2. Ulcerated scaly erythematous plaque of left popliteal area.
Persian Gulf area may be infected with leishmaniasis.7 In recently reported cases, the distribution of lesions was more common on exposed areas of the skin. Lesions were most frequently noted on the upper and lower extremities followed by the trunk, back, and face. The initial lesions are at the site of sandfly bites. The incubation period can be from weeks to months after the initial infection. Clinically, the lesions begin as a nontender, nonpruritic, erythematous papules. They may be wet or dry and become fibrotic or hyperkeratotic with healing. In addition, there may be eczematous, psoriasiform, varicelliform, or verrucous qualities noted. Gradually, lesions tend to widen in size and develop serous crusting and ulceration. Granuloma formation typically ensues giving the lesion raised borders and an erythematous ridge, which is referred to as the ‘‘volcano sign.’’ The surrounding area may exhibit lymphangitic spread with palpable cords and subcutaneous nodules. Secondary bacterial infection may complicate the picture. There are usually no associated systemic symptoms.1,3,8 After infection, adequate immunologic response eliminates the parasite and species-specific immunity results. This immunity has not been shown to be absolute and reinfection is possible. There is limited cross-reactivity in some cases.1 The extent and presentation of disease depend on several factors, including the humoral and cell-mediated immune response of the host, the virulence or the infecting species, and the parasite burden.8 In the cases we have seen at our facility, the initial diagnosis could be made on the cytologic touch preparation alone. Confirmation was made by H&E and PCR. Speciation was possible by culture or PCR. Several other cases were ruled out after evaluation at WRAIR. None of the latter cases showed evidence of leishmaniasis on cytology or H&E initially at our facility. Recent guidance from WRAIR and the
Pehoushek, Quinn, and Crum S199
Fig 4. Tissue macrophages with multiple intracellular organisms. Note that each organism contains nucleus and smaller kinetoplast. (Touch preparation stained with Diff Quik; original magnification: 3600.)
Armed Forces Institute of Pathology (AFIP) has recommended that a scraping be performed at the base of the ulcer of the lesion with a No. 15 blade. A thin layer of the material obtained from this scraping is then evenly smeared on glass slides for Diff-Quik staining and the slide is then interpreted locally. For any nondiagnostic cases, the stained slides and a portion of ethanol-preserved scraping material are to be submitted to the AFIP for review and PCR analysis. Based on the experience at our facility, it is also advisable to obtain tissue in the form of a 4-mm punch biopsy specimen for routine H&E pathologic evaluation to rule out conditions other than leishmaniasis. A single punch biopsy specimen can easily be used to obtain enough material for touch preparation, H&E, and PCR. With the appropriate staining solutions, a preliminary diagnosis can be made in a matter of minutes in much the same way as a potassium hydroxide or Tzanck preparation. (For more information on Leishmania testing, contact the CDC’s Division of Parasitic Diseases at (770) 488-4475.) Although the diagnosis of leishmaniasis must be considered for patients with the appropriate history, experience has shown that other diagnostic considerations should be kept in mind. The differential diagnoses of cutaneous leishmaniasis include cutaneous malignancies, other infectious causes, and a variety of inflammatory dermatoses reactions.1,8 The decision to treat leishmaniasis is based on various factors. Old World cutaneous leishmaniasis tends to resolve spontaneously and the indications for treatment include lesions that are disfiguring, painful, infected, over joints, or slow to heal.1,8 Several therapies are currently available in the United States.9 Pentavalent antimony treatment is available in the form of sodium stibogluconate
S200 Pehoushek, Quinn, and Crum
(Pentostam). WRAMC and Brook Army Medical Center in San Antonio, Tex, are currently providing treatment to all military personnel with sodium stibogluconate under an ongoing treatment protocol. It is also available from the Centers for Disease Control and Prevention as an investigational drug.8 The experience with sodium stibogluconate from WRAMC has shown the most common side effects to be chemical pancreatitis, myalgia, rash, and elevated transaminases.10 Meglumine antimonate (Glucantime) is another pentavalent antimony therapy option that is currently licensed for use in France. Other therapy options for cutaneous leishmaniasis include Dapsone and ketoconazole. Topical paromomycin is showing promise for cutaneous disease from L mexicana but is not available in the United States at this time. There are currently no Food and Drug Administration (FDA)-approved vaccines or prophylactic medications available.8 Additional therapies that have shown potential efficacy for treating cutaneous leishmaniasis are cryotherapy and thermosurgery. In a study conducted in Amman, Jordan, liquid nitrogen was applied to active lesions with a cotton swab for 15 to 20 seconds with a 1-minute thaw and repeated once. A series of up to 3 treatments was given at 3-week intervals. Of 215 patients seen in follow-up, all but one was noted to have significant clinical response.11 In another study, 201 patients were treated with a localized current field-radio frequency device to deliver a single treatment of a 30-second application of 508C heat to active lesions. At 8 weeks follow-up of 191 patients, total cure was noted in 90% of the patients (L mexicana was noted to be the most common causative organism for the disease in this area).12 Thermosurgery is FDA approved for the treatment of cutaneous leishmaniasis. The US Army is acquiring the equipment to provide thermosurgery therapy. Although most physicians, and particularly dermatologists, are aware of leishmaniasis, it is not a common diagnosis in most practices in the United States. As military personnel strengths increasingly rely on reserve soldiers for missions abroad, the occurrence of diseases acquired during military operations will become more commonplace in the civilian medical practice. As a result, civilian medical providers will need to expand their ability to identify,
J AM ACAD DERMATOL NOVEMBER 2004
diagnose, and treat conditions such as leishmaniasis and others, which typically are limited to other areas of the globe. The cases presented in this article emphasize the importance in obtaining an appropriately detailed history and physical examination. It is clear that as our world becomes ‘‘smaller,’’ our differential diagnoses must become more expansive. REFERENCES 1. Keeling JH. Tropical parasitic infections. In: James WD, editor. Textbook of military medicine. Part III, disease and the environment, military dermatology. Washington (DC): Office of The Surgeon General at TMM Publications Borden Institute Walter Reed Army Medical Center; 2003. p. 256-63. 2. Centers for Disease Control and Prevention—Division of Parasitic Diseases. Fact sheet—Leishmania infection (leishmaniasis). Available from:URL:http://www.cdc.gov/ncidod/dpd/ parasites/leishmania/factsht_leishmania.htm. Accessed January 11, 2004. 3. World Health Organization information fact sheet. The leishmaniases and Leishmania/HIV co-infections. Available from: URL:http://www.who.int/inf-fs/en/fact116.html. Accessed January 11, 2004. 4. Centers for Disease Control and Prevention. Viscerotropic leishmaniasis in persons returning from Operation Desert Storm—1990-1991. MMWR Morb Mortal Wkly Rep 1992;41: 131-4. 5. Centers for Disease Control and Prevention. Cutaneous leishmaniasis in US military personnel—Southwest/Central Asia, 2002e2003. MMWR Morb Mortal Wkly Rep 2003;52: 1009-12. 6. Reithinger R, Mohsen M, Aadil K, Sidiqi M, Erasmus P, Coleman PG. Anthroponotic cutaneous leishmaniasis, Kabul, Afghanistan. Emerg Infect Dis 2003;9:727-9. 7. Dooley DP. Great planes regional medical command leishmaniasis briefing. Brook Army Medical Center, Fort Sam Houston, Texas. February 18, 2004. 8. Stark CG, Wortmann G. Leishmaniasis. eMedicine.com. Available from: URL: http://www.emedicine.com/med/topic1275.htm. Accessed December 18, 2003. 9. Abramowicz M, editor. Drugs for parasitic infections. The medical letter on drugs and therapeutics. Available from: URL: http://www.medletter.com. Accessed April 12, 2002. 10. Wortmann G, Miller RS, Oster C, Jackson J, Aronson N. A randomized, double-blind study of the efficacy of a 10- or 20-day course of sodium stibogluconate for treatment of cutaneous leishmaniasis in United States military personnel. Clin Infect Dis 2002;35:261-7. 11. al-Majali O, Routh HB, Abuloham O, Bhowmik KR, Muhsen M, Hebeheba H. A 2-year study of liquid nitrogen therapy in cutaneous leishmaniasis. Int J Dermatol 1997;36:460-2. 12. Velasco-Castrejon O, Walton BC, Rivas-Sanchez B, Garcia MF, Lazaro GJ, Hobart A, et al. Treatment of cutaneous leishmaniasis with localized current field (radio frequency) in Tabasco, Mexico. Am J Trop Med Hyg 1997;57:309-12.