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Recombinant granulocyte colony-stimulating factor for dapsone-induced agranulocytosis in leukocytoclastic vasculitis
Journal of the American Academy of Dermatology Volume 28, Number 4
DNA adducts by the bathwater PUVA therapy or, alternatively, to an ineffective conversioninto crosslinks by subsequent UVA exposures. REFERENCES 1. Lowe NJ, Weingarten D, BourgetT, et al. PUVA therapy for psoriasis: comparison of oral and bath-water delivery of 8-methoxypsoralen. J AM ACAD DERMATOL 1986;14:75460.
Briefcommunications 659 2. Henseler T, WolffK,Honigsmann H, et al.OraI8-methoxypsoralen photochemotherapy for psoriasis: the European PUVA study: a cooperative studyamong18 European centers. Lancet 1981;1:853-7. 3. Ortel B, Maytum DJ, Gange RW. Long persistence of monofunctional 8-methoxypsoralen-DNA adducts in human skinin vivo. Photochem PhotobioI1991;54:645-50.
Recombinant granulocyte colony-stimulating factor for dapsone-induced agranulocytosis in leukocytoclastic vasculitis Sachiko Miyagawa, MD,a Yuko Shiomi, MD,a Takaya Fukumoto, MD,a Yoshiko Ishii, MD,b and Toshihiko Shirai, MDa Nara, Japan Drug-induced neutropenia and its most severe form, agranulocytosis, are potentially lethal. Recombinant granulocyte colony-stimulating factor (G-CSF) is important in the treatment of chemotherapy-induced neutropenia. However, experience with treating drug-induced agranulocytosis with G-CSF is limited. I, 2 We successfullyused G-CSF in a patient with dapsone-induced agranulocytosis. CASE REPORT
A 16-year-old girlhad an 8-week history ofnodules and ulcerson both legs. Examination revealed manynodules with ulceration, mainlyonthe flexor aspect ofher leftleg (Fig. I). Other lesions werepurpura, blisters, and livedo reticularis bilaterally. The patient had no systemic manifestations. Laboratory data indicating abnormality included an erythrocyte sedimentation rate of 44 mm/hr, hypergammaglobulinemia of 29.4% with a serum IgG of 2804 mg/dl (normal 780 to 1450 mg/dl). The rheumatoid factor was 42U Iml (normal< 15U Iml), and C-reactive proteinwas2.9 mg/dl (normal<0.7 mg/dl). Fluorescent antinuclear antibodies and anti-UIRNP antibodies were positive in titers of 1:2560 and 1:20, respectively. Fromthe Departmentof Dermatology, a and Second Department ofInternal Medicine," Nara MedicalUniversity. Reprint requests: Sachiko Miyagawa, MD, Department of Dermatology,Nara MedicalUniversity, Kashihara City,Nara 634,Japan. JAM ACAD DERMATOL 1993;28:659-61. Ccpyright w 1993 by the AmericanAcademyof Dermatology, Inc. 0190-9622/93 $1.00+ .10 16/54/42826
A biopsy specimen from a nodule on the right legrevealed a marked perivascular infiltrate ofneutrophilswith focal hemorrhage and nuclear debris in the dermis. Immunofluorescence microscope studies revealed nodeposition of immunoglobulins or complement components in involved dermal vessel walls. A diagnosis of leukocytoclastic vasculitis was made, andtreatmentwasstartedwith oraldapsone, 50mgdaily. Within a week no new lesions appeared and the patient remained well for 4 weeks. Throughout the course of dapsone treatment routine blood cell counts and urinalyses were normal. The reticulocyte counts ranged from 0.8% to 2.6%. On the twenty-ninth day of dapsone therapy, the leukocytecount was1500/mm3, with32% neutrophils, 65% lymphocytes, and 3% monocytes inthe differential count. Dapsone was stopped. On thethirty-second day, however, her leukocyte countwas 1200/mm3 with no neutrophils, 83% lymphocytes, 17% monocytes, hematocrit 29.6%, hemoglobin 9.8 gm/dl, and platelets 21.5 X 104/mm3 (day 0). Bone marrow examination revealed hypoplasia (l8,000/mm3 nucleated marrow cells) and maturation arrestofmyeloid cells. The myeloid elements were 26001 mm! with 39% myeloblasts, 44% promyelocytes, 11% myelocytes, 3% metamyelocytes, 3% basophils, and no neutrophils. Erythroid and megakaryocytic series had a normal appearance. G-CSF, 125 f.Lg (3.2 f.Lg/kg) daily, wasadministered subcutaneously for 6 days. Theneutrophil and immature granulocyte counts increased rapidly from 80/mm3 (afteronetreatment) to 13,000/mm3 (after sixtreatments). No effect on the platelet or erythrocytecounts was found. Aftertreatmentwas discontinued, leukocyte counts gradually returned to normal. On day8
660 Brief communications
Fig. 1. Hemorrhagic blisters and ulcers on patient's leg. the myeloid elements in the bone marrow reached a level of 22.6 X 104/ mm 3 (82.8% of nucleated bone marrow cells). No toxicity ascribable to G-CSF was noted. A drug lymphocyte transformation test 3 for dapsone gave a negative finding. With intravenous ceftizoxime sodium, 2 gm/day, and clindamycin phosphate, 600 mg.' day, for 10 days to protect her from infection during the period of agranulocytosis, the patient recovered completely. Her vasculitis reappeared in 2 weeks and has been controlled by prednisolone, 10 mg/day, as maintenance therapy. A glucose-e-phosphate-dehydrogenase blood level was normal.
DISCUSSION Recently dapsone has proved to be remarkably effective and relatively safe in the treatment of leukocytoc1astic vasculitis.v'' Cases of agranulocytosis have previously been described in patients treated with dapsone for dermatitis herpetiformis and other cutaneous diseases and for the prophylaxis of malaria. Usually, dapsone-induced agranulocytosis lasts 1 to 2 weeks after cessation of dapsone and sometimes is fata1.?,8 Until recently no definitive therapy has been available. With the introduction of human recombinant granulocyte and granulocyte/macrophage colonystimulating factors (G-CSF and GM-CSF), it has been possible to treat several forms of neutropenia, including congenital disorders, aplastic anemia, and
Journal of the American Academy of Dermatology April 1993
chemotherapy-induced neutropenia. These factors are also increasingly used to treat drug-induced agranulocytosis.': 2, 9-!3 Case reports have shown that rapid recovery in patients with severe depression ofbone marrow granulopoiesis is most likely induced by therapy with G-CSF or GM-CSF. Cutaneous disorders characterized by dermal infiltration with mature neutrophils have been described as adverse reactions to G-CSF or GM-CSF. Glaspy et a1.!4 described a patient with hairy cell leukemia and cutaneous vasculitis who after G-CSF treatment had Sweet's syndrome. Kluin-Nelemans et a1. 15 reported the case of a patient in whom leukocytoc1astic vasculitis developed after 4 days of treatment with GM-CSF for severe neutropenia. They concluded that a latent tendency to develop leukocytoclastic vasculitis had been provoked by GM-CSF treatment in their case. We believe that G-CSF expedited the recovery of granulocyte counts in our patient without adverse reactions and warrants further study in the management of drug-induced neutropenia. REFERENCES 1. MuroiK,Ito M,SasakiR, etal. Treatmentofdrug-induced agranulocytosis with granulocyte-colony stimulating factor. Lancet 1989;2:55. 2. EllmanMH, TelferMC, TurnerAF. Benefit ofG-CSF for methotrexate-induced neutropenia in rheumatoid arthritis. Am J Med 1992;92:337-8. 3. Dobozy A, Hunyadi J, Simon N. Lymphocyte-transformation test in detection of drug hypersensitivity. Lancet 1972;2:1319.
4. Fredenberg MF, Malkinson FD. Sulfone therapy in the treatment of leukocytoclastic vasculitis. J AM ACAD DERMATOL 1987;16:772-8. 5. Katz SI, Gallin Jl, Hertz KC, et al. Erythema elevatum diutinum: skin and systemic manifestations, immunologic studies and successful treatment with dapsone. Medicine 1977;56:443-55.
6. Fortson JS, Zone JJ, Hammond ME, et al. Hypocomplementemic urticarialvasculitis syndrome responsive to dapsone. J AM ACAD DERMATOL 1986;15:1137-42. 7. Potter MN, YatesP, SladeR, et al.Agranulocytosis caused by dapsone therapy for granuloma annulare. J AM ACAD DERMATOL 1989;20:87-8. 8. Hornsten P, Keisu M, Wiholm B-E. The incidence of agranulocytosis during treatment of dermatitis herpetiformis with dapsone as reported in Sweden, 1972 through 1988. Arch Dermatol 1990;126:919-22. 9. Delannoy A, Gehenot M. Colony-stimulating factor and drug-induced agranulocytosis [Letter]. Ann Intern Med 1989;110:942-3.
10. Heinrich B, Gross M, Goebel FD. Methimazole-induced agranulocytosis and granulocyte colony-stimulating factor [Letter]. Ann Intern Med 1989;1l1:621-2. II. PalmbladJ, Jonson B, Kanerud L. Treatment of drug-in-
Journ al of the American Academ y of Dermatology Volume 28, Number 4
duce d agra nulocytosis with recomb inant GM -CSF. J Intern Moo 1990;228:537-9. 12. N and S, Ba yer R , Prinz RA, et a l. Granulocyte macropha ge colony-stimulating factor for the treatmen t of drug indu ced agranulocytosis. Am J HematolI991 ;37:267-9. 13. Wallach FR, Zirn J ,Murra y HW, eta!' Use of granulocyte macrophage colony-stimulati ng factor for treatment of dr ug-induced agra nulocytosis [Le tter] . RID 1991;13:523.
Brief communications 661 14. Glaspy JA, Bal dwin GC, Robertson PA, et al. Therapy for neutropenia in hairy cell leukemia with recombinant human granulocyte colony-stimula ting fact or. Ann Intern Med 1988;109:789-95. 15. Kluin-Nelemans J'C , Holla nder A AMJ, F ibbe WE, et al. Leucocytoclastic vasculitis during GM-CSF therapy. Br J Haematol 1989;73:4 19-20.
Lip leishmaniasis Kbaled El-Hoshy, MD Durham, North Carolina Cutaneous leishmaniasis of the Old World is caused by at least three subspecies of Leishmania tropica and is transmitted by sand fly bites.1 The disease occurs in the Middle East, Medi terranean basin, and parts of Afric a. The gulf war sparked interest in this disease.i This report describes lip leishmaniasis, a common yet rarely mentioned manifestation of cutaneous
leishmaniasis ' CASE PRESENTATIONS
Seventy-two cases of cutaneous leishmaniasis were seen in 2 years in a referral hospital in southern Saudi Arabia. Twelve patients had lip swelling or ulceration of either the upper or lower lip. The patients' ages ranged from 3 to 40 years. Duration ranged from I to 8 months. Ten patients had only lip lesions, whereas two patients had a second lesion elsewhere. The lesions were firm, tender nodules, often with a small ulcer or crust usually involvingthe vermi lion border ( Fig. 1). Nodule size varied from 0.5 to 2.5 ern in diameter (F ig. 2). There were no palpable lymph nodes, and the general health was not affected. Most ga ve a history of failure to respond to systemic antibiotic thera py. The diagnosis was confirmed by Giems a-stained smears . Tr eatment with liquid nitrogen as the sole therapy was effective in only 2 of the 12 patients. In the other paFrom the Dermal ologic Su rgery Unit, D ivision of Dermatology, DUke University Medic al Ce nter.
Presented in part at the Forty-ninth Annual Meeting of tile American Academy of Dermatology, At lanta, Oa ., Dec. 1-6, 1990. N o reprints ava ilable. J AM A CAD DERMATOL
1993;28:661-2.
Copyright ® 1993 by the American Academy of Dermatology, Inc. 0190-9622/93 $1.00
+ .10
16/54/42414
Fig. 1. Crusted nodule on upper lip, left side. tients, an intramuscular pentavalent antimonial (Pentostam ), 10 mg/kg, was given every day or every other day for a total of 10 injections. In three cases a second course was needed for complete resolution. Ketoconazole, 200 mg/day, for 4 weeks was used in three children with no improvement; they were later treated with the intramuscular antimonial. DISCUSSION
Lip swelling is seldom mentioned as a presentation of cutaneous leishmaniasis despite its relatively common occurrence, as seen in this series (16.7%).4 The clinical differential diagnosis, depending on the disease duration, includes herpes labialis, impetigo, trauma, fixed drug eruption, syphilitic chancre, Melkersson-Rosenthal syndrome, granulomatous cheilitis, sarcoidosis, lymphedema (pos tinfective), lymphangioma, hemangioma, mucous cyst.Ieprosy, tuberculosis, or squamous cell carcinoma. The diagnosis is easier to make if typical cutaneous leishma-
DNA adducts by the bathwater PUVA therapy or, alternatively, to an ineffective conversioninto crosslinks by subsequent UVA exposures. REFERENCES 1. Lowe NJ, Weingarten D, BourgetT, et al. PUVA therapy for psoriasis: comparison of oral and bath-water delivery of 8-methoxypsoralen. J AM ACAD DERMATOL 1986;14:75460.
Briefcommunications 659 2. Henseler T, WolffK,Honigsmann H, et al.OraI8-methoxypsoralen photochemotherapy for psoriasis: the European PUVA study: a cooperative studyamong18 European centers. Lancet 1981;1:853-7. 3. Ortel B, Maytum DJ, Gange RW. Long persistence of monofunctional 8-methoxypsoralen-DNA adducts in human skinin vivo. Photochem PhotobioI1991;54:645-50.
Recombinant granulocyte colony-stimulating factor for dapsone-induced agranulocytosis in leukocytoclastic vasculitis Sachiko Miyagawa, MD,a Yuko Shiomi, MD,a Takaya Fukumoto, MD,a Yoshiko Ishii, MD,b and Toshihiko Shirai, MDa Nara, Japan Drug-induced neutropenia and its most severe form, agranulocytosis, are potentially lethal. Recombinant granulocyte colony-stimulating factor (G-CSF) is important in the treatment of chemotherapy-induced neutropenia. However, experience with treating drug-induced agranulocytosis with G-CSF is limited. I, 2 We successfullyused G-CSF in a patient with dapsone-induced agranulocytosis. CASE REPORT
A 16-year-old girlhad an 8-week history ofnodules and ulcerson both legs. Examination revealed manynodules with ulceration, mainlyonthe flexor aspect ofher leftleg (Fig. I). Other lesions werepurpura, blisters, and livedo reticularis bilaterally. The patient had no systemic manifestations. Laboratory data indicating abnormality included an erythrocyte sedimentation rate of 44 mm/hr, hypergammaglobulinemia of 29.4% with a serum IgG of 2804 mg/dl (normal 780 to 1450 mg/dl). The rheumatoid factor was 42U Iml (normal< 15U Iml), and C-reactive proteinwas2.9 mg/dl (normal<0.7 mg/dl). Fluorescent antinuclear antibodies and anti-UIRNP antibodies were positive in titers of 1:2560 and 1:20, respectively. Fromthe Departmentof Dermatology, a and Second Department ofInternal Medicine," Nara MedicalUniversity. Reprint requests: Sachiko Miyagawa, MD, Department of Dermatology,Nara MedicalUniversity, Kashihara City,Nara 634,Japan. JAM ACAD DERMATOL 1993;28:659-61. Ccpyright w 1993 by the AmericanAcademyof Dermatology, Inc. 0190-9622/93 $1.00+ .10 16/54/42826
A biopsy specimen from a nodule on the right legrevealed a marked perivascular infiltrate ofneutrophilswith focal hemorrhage and nuclear debris in the dermis. Immunofluorescence microscope studies revealed nodeposition of immunoglobulins or complement components in involved dermal vessel walls. A diagnosis of leukocytoclastic vasculitis was made, andtreatmentwasstartedwith oraldapsone, 50mgdaily. Within a week no new lesions appeared and the patient remained well for 4 weeks. Throughout the course of dapsone treatment routine blood cell counts and urinalyses were normal. The reticulocyte counts ranged from 0.8% to 2.6%. On the twenty-ninth day of dapsone therapy, the leukocytecount was1500/mm3, with32% neutrophils, 65% lymphocytes, and 3% monocytes inthe differential count. Dapsone was stopped. On thethirty-second day, however, her leukocyte countwas 1200/mm3 with no neutrophils, 83% lymphocytes, 17% monocytes, hematocrit 29.6%, hemoglobin 9.8 gm/dl, and platelets 21.5 X 104/mm3 (day 0). Bone marrow examination revealed hypoplasia (l8,000/mm3 nucleated marrow cells) and maturation arrestofmyeloid cells. The myeloid elements were 26001 mm! with 39% myeloblasts, 44% promyelocytes, 11% myelocytes, 3% metamyelocytes, 3% basophils, and no neutrophils. Erythroid and megakaryocytic series had a normal appearance. G-CSF, 125 f.Lg (3.2 f.Lg/kg) daily, wasadministered subcutaneously for 6 days. Theneutrophil and immature granulocyte counts increased rapidly from 80/mm3 (afteronetreatment) to 13,000/mm3 (after sixtreatments). No effect on the platelet or erythrocytecounts was found. Aftertreatmentwas discontinued, leukocyte counts gradually returned to normal. On day8
660 Brief communications
Fig. 1. Hemorrhagic blisters and ulcers on patient's leg. the myeloid elements in the bone marrow reached a level of 22.6 X 104/ mm 3 (82.8% of nucleated bone marrow cells). No toxicity ascribable to G-CSF was noted. A drug lymphocyte transformation test 3 for dapsone gave a negative finding. With intravenous ceftizoxime sodium, 2 gm/day, and clindamycin phosphate, 600 mg.' day, for 10 days to protect her from infection during the period of agranulocytosis, the patient recovered completely. Her vasculitis reappeared in 2 weeks and has been controlled by prednisolone, 10 mg/day, as maintenance therapy. A glucose-e-phosphate-dehydrogenase blood level was normal.
DISCUSSION Recently dapsone has proved to be remarkably effective and relatively safe in the treatment of leukocytoc1astic vasculitis.v'' Cases of agranulocytosis have previously been described in patients treated with dapsone for dermatitis herpetiformis and other cutaneous diseases and for the prophylaxis of malaria. Usually, dapsone-induced agranulocytosis lasts 1 to 2 weeks after cessation of dapsone and sometimes is fata1.?,8 Until recently no definitive therapy has been available. With the introduction of human recombinant granulocyte and granulocyte/macrophage colonystimulating factors (G-CSF and GM-CSF), it has been possible to treat several forms of neutropenia, including congenital disorders, aplastic anemia, and
Journal of the American Academy of Dermatology April 1993
chemotherapy-induced neutropenia. These factors are also increasingly used to treat drug-induced agranulocytosis.': 2, 9-!3 Case reports have shown that rapid recovery in patients with severe depression ofbone marrow granulopoiesis is most likely induced by therapy with G-CSF or GM-CSF. Cutaneous disorders characterized by dermal infiltration with mature neutrophils have been described as adverse reactions to G-CSF or GM-CSF. Glaspy et a1.!4 described a patient with hairy cell leukemia and cutaneous vasculitis who after G-CSF treatment had Sweet's syndrome. Kluin-Nelemans et a1. 15 reported the case of a patient in whom leukocytoc1astic vasculitis developed after 4 days of treatment with GM-CSF for severe neutropenia. They concluded that a latent tendency to develop leukocytoclastic vasculitis had been provoked by GM-CSF treatment in their case. We believe that G-CSF expedited the recovery of granulocyte counts in our patient without adverse reactions and warrants further study in the management of drug-induced neutropenia. REFERENCES 1. MuroiK,Ito M,SasakiR, etal. Treatmentofdrug-induced agranulocytosis with granulocyte-colony stimulating factor. Lancet 1989;2:55. 2. EllmanMH, TelferMC, TurnerAF. Benefit ofG-CSF for methotrexate-induced neutropenia in rheumatoid arthritis. Am J Med 1992;92:337-8. 3. Dobozy A, Hunyadi J, Simon N. Lymphocyte-transformation test in detection of drug hypersensitivity. Lancet 1972;2:1319.
4. Fredenberg MF, Malkinson FD. Sulfone therapy in the treatment of leukocytoclastic vasculitis. J AM ACAD DERMATOL 1987;16:772-8. 5. Katz SI, Gallin Jl, Hertz KC, et al. Erythema elevatum diutinum: skin and systemic manifestations, immunologic studies and successful treatment with dapsone. Medicine 1977;56:443-55.
6. Fortson JS, Zone JJ, Hammond ME, et al. Hypocomplementemic urticarialvasculitis syndrome responsive to dapsone. J AM ACAD DERMATOL 1986;15:1137-42. 7. Potter MN, YatesP, SladeR, et al.Agranulocytosis caused by dapsone therapy for granuloma annulare. J AM ACAD DERMATOL 1989;20:87-8. 8. Hornsten P, Keisu M, Wiholm B-E. The incidence of agranulocytosis during treatment of dermatitis herpetiformis with dapsone as reported in Sweden, 1972 through 1988. Arch Dermatol 1990;126:919-22. 9. Delannoy A, Gehenot M. Colony-stimulating factor and drug-induced agranulocytosis [Letter]. Ann Intern Med 1989;110:942-3.
10. Heinrich B, Gross M, Goebel FD. Methimazole-induced agranulocytosis and granulocyte colony-stimulating factor [Letter]. Ann Intern Med 1989;1l1:621-2. II. PalmbladJ, Jonson B, Kanerud L. Treatment of drug-in-
Journ al of the American Academ y of Dermatology Volume 28, Number 4
duce d agra nulocytosis with recomb inant GM -CSF. J Intern Moo 1990;228:537-9. 12. N and S, Ba yer R , Prinz RA, et a l. Granulocyte macropha ge colony-stimulating factor for the treatmen t of drug indu ced agranulocytosis. Am J HematolI991 ;37:267-9. 13. Wallach FR, Zirn J ,Murra y HW, eta!' Use of granulocyte macrophage colony-stimulati ng factor for treatment of dr ug-induced agra nulocytosis [Le tter] . RID 1991;13:523.
Brief communications 661 14. Glaspy JA, Bal dwin GC, Robertson PA, et al. Therapy for neutropenia in hairy cell leukemia with recombinant human granulocyte colony-stimula ting fact or. Ann Intern Med 1988;109:789-95. 15. Kluin-Nelemans J'C , Holla nder A AMJ, F ibbe WE, et al. Leucocytoclastic vasculitis during GM-CSF therapy. Br J Haematol 1989;73:4 19-20.
Lip leishmaniasis Kbaled El-Hoshy, MD Durham, North Carolina Cutaneous leishmaniasis of the Old World is caused by at least three subspecies of Leishmania tropica and is transmitted by sand fly bites.1 The disease occurs in the Middle East, Medi terranean basin, and parts of Afric a. The gulf war sparked interest in this disease.i This report describes lip leishmaniasis, a common yet rarely mentioned manifestation of cutaneous
leishmaniasis ' CASE PRESENTATIONS
Seventy-two cases of cutaneous leishmaniasis were seen in 2 years in a referral hospital in southern Saudi Arabia. Twelve patients had lip swelling or ulceration of either the upper or lower lip. The patients' ages ranged from 3 to 40 years. Duration ranged from I to 8 months. Ten patients had only lip lesions, whereas two patients had a second lesion elsewhere. The lesions were firm, tender nodules, often with a small ulcer or crust usually involvingthe vermi lion border ( Fig. 1). Nodule size varied from 0.5 to 2.5 ern in diameter (F ig. 2). There were no palpable lymph nodes, and the general health was not affected. Most ga ve a history of failure to respond to systemic antibiotic thera py. The diagnosis was confirmed by Giems a-stained smears . Tr eatment with liquid nitrogen as the sole therapy was effective in only 2 of the 12 patients. In the other paFrom the Dermal ologic Su rgery Unit, D ivision of Dermatology, DUke University Medic al Ce nter.
Presented in part at the Forty-ninth Annual Meeting of tile American Academy of Dermatology, At lanta, Oa ., Dec. 1-6, 1990. N o reprints ava ilable. J AM A CAD DERMATOL
1993;28:661-2.
Copyright ® 1993 by the American Academy of Dermatology, Inc. 0190-9622/93 $1.00
+ .10
16/54/42414
Fig. 1. Crusted nodule on upper lip, left side. tients, an intramuscular pentavalent antimonial (Pentostam ), 10 mg/kg, was given every day or every other day for a total of 10 injections. In three cases a second course was needed for complete resolution. Ketoconazole, 200 mg/day, for 4 weeks was used in three children with no improvement; they were later treated with the intramuscular antimonial. DISCUSSION
Lip swelling is seldom mentioned as a presentation of cutaneous leishmaniasis despite its relatively common occurrence, as seen in this series (16.7%).4 The clinical differential diagnosis, depending on the disease duration, includes herpes labialis, impetigo, trauma, fixed drug eruption, syphilitic chancre, Melkersson-Rosenthal syndrome, granulomatous cheilitis, sarcoidosis, lymphedema (pos tinfective), lymphangioma, hemangioma, mucous cyst.Ieprosy, tuberculosis, or squamous cell carcinoma. The diagnosis is easier to make if typical cutaneous leishma-