January-February 1990, Vol. 29, No. 1
Pharmacology and Therapeutics
Cutaneous Leishmaniasis Treatment with Combined Cryotherapy and Intralesional Stibogluconate Injection M. A. EL DAROUTI, M.D.,
AND S. M . AL RUBAIE, M.D.
From the Department of Dermatology, Rashid Hospital, Dubai, United Arab Emirates
ABSTfiACT: A combination of both intralesional stibogluconate injection and superficial cryotherapy (not including the base of the lesion nor the 1-2 mm rim of the surrounding normal skin) was performed in an attempt to improve the therapeutic efficacy of either of the two modalities when used separately in the treatment of cutaneous leishmaniasis. This combined therapy resulted in a 100% cure rate in 15 patients with 23 lesions of cutaneous leishmaniasis. Two control groups, one treated with superficial cryo and the other treated with intralesional stibogluconate injection alone were included in the study for evaluation. The results obtained by combined superficial freezing and intralesional stibogluconate injection were much more impressive than those obtained by each of the two modalities when used alone.
C
utaneous leishmaniasis is a specific granuloma of the skin caused by Leishmania tropica,^ and is commonly seen in tropical and subtropical areas. After an incubation period ranging from few weeks to few months it starts as a furunclelike papule that in time enlarges and frequently ulcerates and finally heals within approximately one year, leaving behind a characteristic, permanent, depressed and disfiguring
anaphylactold reaction. Headache, vomiting, fainting, arrythmias, seizures, and muscle and joint pain are common side effects of parenterally administered antimonial preparations.' Intralesional injections of pentavalent antimonials may be effective and are preferred for the localized cutaneous lesions of leishmaniasis because of fewer side effects than the parenterally administered antimonials.'' Unfortunately, when used alone complete recovery is not the rule. Cryotherapy was found useful in the treatment of localized cutaneous leishmaniasis.''^ Extensive freezing of the lesions is destructive, painful, and the damage produced by it may be slow to heal. Light freezing is better tolerated by the patient but is not equally effective. In this study, a combination of both intralesional antimonial injection and superficial freezing was tried on a group of 15 patients in an attempt to improve the efficacy of each of the two modalities when used alone. Patients and Methods Fourty-four patients, 19 women and 25 men with a mean age of 32 years, were included in this study (Table 1); tbere were 60 lesions of leisbmaniasis studied. Tbe mean duration of lesions was 9 weeks, and the mean size was 3 cm. Ulcerations were seen in 18 lesions. Eight of tbe lesions were associated witb tbe development of satellites. The most frequently affected sites were the lower limbs (28 lesions) and upper limbs (22 lesions). Tbe face was less frequently involved (8 lesions), and only two lesions were found on the back. Biopsy specimens were taken from 45 lesions. Early lesions and nonulcerated areas of ulcerated lesions were chosen for biopsy to increase tbe possibility of detecting tbe organisms. Microscopic features showed granulomas witb numerous macropbages, plasma cells, and lympboid cells. Polymorpbs and esinopbils were seen in variable numbers. Tbe causative organisms (leisbmania donovan bodies) ap-
Pentavalent antimonials such as meglumine antimonate (glucantime) or sodium stibogluconate (pentostam) still form the basis for all treatment of leishmaniasis; however, they should be used with care particularly when administered via intravenous or intramuscular routes. They tend to accumulate and are excreted slowly. They may cause cardiac, hepatic, renal, and cerebral toxicity and can precipitate an Address for correspondence: M. A. El Darouti, Department of Dermatology, Rashid Hospital, Dubai, United Arab Emirates.
56
No. 1
CUTANEOUS LEISHMANIASIS
TABLE 1. Basic and Case History Data Group 1 Number of patients Dropouts Number of cases evaluated
18
3 15
Croup 2 17 3
Croup 3 19
14
4 15
9
8
8
6
6
7
32
30.5
32.5
23 10
19
18 9.5
10
9
9
9
7
6
3 1
3 —
2 1
7
5 2
2
Sex
Men Women Age (years, mean) Number of lesions (mean) Duration (weeks, mean) Sites of lesions Legs Arms Face Back Ulceration Satellite lesions Size of lesion (cm, mean) Biopsy Organisms detected with H & E Organisms detected with Ciemsa Pretreatment Yes No
9
4 3.5 15 5 8
2.5 15 4 9
—
—
15
15
6 3 15 5
El Darouti and At Ruhaie
57
tbe cartridge dental syringe to minimize tbe pain and allow easier infiltration of tbe lesions. Tbe lesions were examined weekly for 6 weeks. Signs of improvement such as diminusion in size, healing of tbe ulceration, flattening, and fading of color were recorded. Tbe second group (14 patients witb 19 lesions) was treated witb cryotberapy alone using superficial freezing in tbe same way as tbe first group. Results of therapy were recorded every week for 6 weeks. Patients of tbe tbird group (15 patients with 18 lesions) were treated by intralesional injection of stibogluconate every otber day for 10 injections. Tbe drug was administered in tbe same way as in the first group. Signs of improvement were registered every week for 6 weeks. After fhe end of tbe treatment period (6 weeks) all groups of patients were examined every month for any signs of recurrence and for evaluation of tbe side effects sucb as depigmentation and scarring. Tbe final evaluation was done 3 montbs after conclusion of tberapy. Results were analyzed using student's t test. Results
7 — 15
peared as intracellular and extracellular circular or ovoid bodies. Leishmania donovan bodies were detected easily by bematoxylin and eosin stain in 14 of tbe specimens. Ciemsa stain was needed for tbe clarification of tbe organisms in 24 specimens. Liver and renal function tests and an ECG were assessed for all tbe patients. Ten patients were excluded from tbe study either because of abnormalities of liver and/or renal function tests (3 patients), or because of failure of compliance (7 patients). Treatment Pafienfs were divided into three groups. Patients in tbe first group (15 patients witb 23 lesions) were treated by combined cryotberapy and intralesional stibogluconate injection. Lesions were subjected to superficial freezing using liquid nitrogen probe (Spembly cryo surgery system DFS 30, Spembly Ltd, Hampsbire, England). Lubricating jelly was applied to the lesions before freezing to achieve better contact between fbe cryo probe and tbe surface of the lesion. Freezing was continued for 10 seconds only (until tbe surface turned wbite). Care was taken to avoid freezing of tbe bases of the lesions and tbe surrounding 1-2 mm of tbe normal skin. Edema and/or bullae formation always followed within 8-12 bours. Patients were instructed to apply saline compresses three times a day until a crust forms and dries up (usually 1-2 weeks). Thereafter antibiotic creams were applied to belp remove tbe crust. Freezing was repeated three times, once every 2 weeks. Intralesional stibogluconate (2-5 ml according to the size of tbe lesion) was injected every otber day. Tbe first injection was given immediately after tbe first session of cryo (following tbawing of tbe lesion) and was repeated every other day for 10 injections. Stibogluconate was injected by
The results are illustrated in Table 2. All patients of the first group, treated with combined cryo therapy and intralesional stibogluconate injection were cured after 6 weeks from the start of therapy. Nineteen lesions (82%) were cured after 4 weeks and needed no further therapy. Small and nonulcerative lesions showed a remarkably rapid response, while large, ulcerative lesions and lesions on the lower limbs took longer to heal. Healing was associated with temporary hypopigmentation in 19 lesions, ie, 82% of the cases. Darkskinned patients were more prone to this side effect. Complete repigmentation, which started with perifollicular darkening, occurred in 8-12 weeks. Minimal scarring was present at the site of 30% (7) of the lesions; all such lesions were ulcerative. In the second group (treated with cryo alone) 11 patients, with 13 lesions (68% of the patients) were completely cured by the end of the 6th week, ie, 2 weeks after the last cryo session. As in the first group, small and nonulcerated lesions responded better to treatment. Lesions on the lower limbs responded more slowly than lesions elsewhere. Temporary depigmentation occurred at the site of 16 (84%) of the lesions. Nonetheless, complete repigmentation was evident after 3 months. Minimal scarring occurred in six (31%) of the lesions; it was seen more frequently in association with ulceration. In the third group, treated with intralesional pentostam injection alone, only six patients (with eight lesions) were cured. The cure rate was 44%. There were no systemic side effects to the intralesional injection of stibogluconate. Scarring occurred in
58
INTERNATIONAL JOURNAL OE DERMATOLOGY TABLE 2.
Number of Patients Number of lesions Treatment
Healing After 4 weeks After 6 weeks Side effects Reversible hypopigmentation Scarring E.C.G. Liver or renal abnormalities
January-February 1990
Vol. 29
Results of Treatment of Leishmaniasis with Comhined Cryo and Intralesional Stihogluconate Injection and with either Modalities Civen Alone Group 1
Group 2
Group 3
15 23 Combined superficial cryotherapy and intralesional pentostam injections
14 19 Superficial cryotherapy
15 18 Intralesional stibogluconate injection
19 (82%) 23 (100%)
10(52%) 13 (68"/o)
6 (33%) 8 (44%)
19 (82%) 7 (30%)
16 (84'y()) 6 (31%)
10(55%)
ten (55%) of the lesions and was more commonly seen at the sites of ulcerations. The overall results showed clearly that the combined freezing and intralesional stibogluconate injection was superior to either cryotherapy or intralesional stibogluconate injection when given separately. The difference in results were statistically significant (p
Discussion
Despite the introduction of many drugs in the treatment of leishmaniasis such as ketoconazole,^ dapson,^''' rifampicin and antimalarials,^ pentavalent antimonials are still the most widely used drugs. The parenteral administration of pentavalent antimonials, however, may be associated with side effects such as electrocardiographic changes (depressed T wave and conduction defects), transaminase rise, and acute renal insufficiency." Nevertheless, these complications usually are not encountered if the drugs are given intralesionally. One course of intralesional injections may not be sufficient and more than one course will be needed. In this study intralesional injection of stibogluconate was effective only in 44% of the cases when it was used alone. This result, however, reached 100% when intralesional stibogluconate injection was combined with freezing; a second course was never required. The increased efficacy of intralesional antimonial injections when it was combined with freezing could be attributed to either a synergistic effect of both lines of therapy or, alternatively, to the possibility that cryo, causing disturbances in the wall permiability"* of the macrophages harboring the organisms, results in a
better accessability of the antimonials inside the macrophages where the concentration of leishmania donovan bodies is maximum. Deep freezing of the leishmania lesions, ie, until the whole lesion and a 1-2 mm margin around it is frozen'"'" is probably not necessary, as deep freezing is not devoid of side effects.'^ The edema and/or bullous lesions that follow deep freezing usually take a long time to heal and may result in the formation of unsightly scarring. Moreover, permanent depigmentation, particularly in patients with dark complexions, is more commonly seen after deep freezing. Deep freezing in certain localities, such as over the shins, is better avoided. We have found light freezing in the treatment of leishmaniasis to be equally effective and not associated with the side effects that would occur with the use of deep freezing. Healing time and depigmentation after light freezing, in our experience, took a remarkably shorter time than that required for the lesions produced by deep cryo, and scarring was absent or minimal. The combination of both light cryotherapy and intralesional injection of pentavalent antimonials is more effective in the treatment of cutaneous leishmaniasis than either cryotherapy or intralesional antimonial injections when used alone. It can be considered a highly effective and safe approach for the treatment of cutaneous leishmaniasis. References 1. Farah ES. Protozoan and Helminth infections. In: Fitzpatrick TB, Eisen AZ, Wolff K, et al, eds. Dermatology in general medicine. 3rd ed. New York: McGraw-Hill, 1987:2477-2507. 2. Harman RR. Parasitic worms and protozoa. In: Rook A, Wilkin-
No. 1
3. 4.
5. 6.
7.
CUTANEOUS LEISHMANIASIS
son, DS, Ebling FJ, et al, eds. Text book of dermatology. 4th ed. Oxford: Blackweli Scientific Publications, 1986:9871031. Moschella SL. Diseases of the mononuclear phagocytic system. In: Moschella SL, Hurley HJ, eds. Dermatology 2nd ed. Philadelphia: WB Saunders, 1985:890-1000. Oliveira Neto .MW, Pirmez C, Coutinho S, et al. Interleslonal pentavalent antimonial therapy in American cutaneous leishmaniasis: a two-year follow-up study. Presented at 17th world congress of dermatology. Berlin: World Congress of Dermatology, 1987. Jolliffe DS. Cutaneous leishmaniasis from Brazile: treatment with ketoconazole. Clin Exp Dermatol. 1986,11:62-68. Dogra JB, Misra NS. Cutaneous leishmaniasis: therapeutic efficacy of dapson in the commonly existing subtypes. Presented at 1 7th world congress of dermatology. Berlin: World Congress of Dermatology, 1987. Jaideep D, Bhupender BL, Shayam NM. Dapson in treatment of cutaneous leishmaniasis. Int J Dermatol. 1986;25:398-400.
El Darouti and A! Rubaie
59
8. Marsden PD. Leishmaniasis cutaneous and mucocutaneous. In: Maddin S, ed. Current dermatologic therapy. Philadelphia: WB Saunders, 1982:268-272. 9. Zacadan SA. Cryogenics: the cryolesion and the pathogenesis of cryonecrosis. In: Zacarian SA, ed. Cryosurgery for skin cancer and cutaneous disorders. St. Louis: C.V. Mosby, 1985:1-31. 10. El Banhawi MO, El Tonsy MH, George WM. Cryosurgery in treatment of cutaneous leishmaniasis. Presented at the 17th World Congress of Dermatology. Berlin: World Congress of Dermatology, 1987. n . Leibovici V, Aram H. Cryotherapy in acute cutaneous leishmaniasis. Intj Dermatol. 1986;25:473-475. 12. Zacarian SA. Complications, indications, and contraindications in cryosurgery. In: Zacarian SA, ed. Cryosurgery for skin cancer and cutaneous disorders. St. Louis: C.V. Mosby, 1985:283-298.
Ayurvedic Dermatology On the subject of leprosy, a well-written book entitled "A Therapeutic Guide to Ayurvedic Medicine", written in 1970 by Pandit R. R. Pathak of India, who was once the Director of the Ayurvedic Research Institute at Navlnna, near Colombo, merits attention. This book is based on ancient Sanskrit ayurvedic texts. In the 25 page chapter on skin diseases or Tvak-vikara he lists about 36 diseases which can be recognized as specific diagnoses. Actiologically, all diseases were considered to be a result of disturbance in the 3 bodily humours which were Vatha or wind, Pitha or bile and Sema or Phlegm. It may seem that these 3 humours are identical with what one normally conceives when these terms are used. For example, "wind" in relation to human physiology would bring to mind such ideas as belching or flatus or even gurgling in the abdomen; "bile" makes us think of nausea or bilious vomiting; and "phlegm" implies a cold or cough with abundant sputum or saliva. However, it is important to realize that though these common terms have been used, the ayurvedic concept of the 3 humours cannot be subject to such simplistic interpretation. All skin disorders were divided into Major and Minor categories. The ancients recognized 7 major skin diseases and 11 minor disorders. On a basis of derangement of the humours, all skin disorders were believed to be a result of fault in one, two or all three of the humours. Thus they concluded that there were 7 aetiological bases for these diseases. The commonest of the 36 skin disorders was eczema. It is noteworthy that tinea versicolor or alu hang (literally "grey skin") was not considered a skin disease, but was admired as providential embellishment termed gomara. Terms to describe clinical features and the appearances of lesions were rather limited but constituted the basis of modern clinical dermatology. The macule and papule, and features such as weeping and dry, were described. On the prophylactic aspect the ancients believed that there were medicines which improved the health of the skin and made it resistant to disease. From the therapeutic viewpoint the basic principle was that the causative humour too must be treated in addition to its manifestations. Among the large number of herbal and other preparations used were several which are recognized as being at least kind to the skin. Many of us have seen or heard of the Kustarajagala in Weligama. It is a granite statue which stands between 88th and 89th mile-posts on the old highway to Galle. Several versions have been written to explain its history and significance since Bennett gave a long account of it in 1843. Kustaraja has been literally translated to mean 'leper king'. As already mentioned the ancients included leprosy among the seven Maha-kushtas, and as to the disease in any particular instance having been leprosy itself is anybody's guess.—Ranasinghe L: Mussings relating to skin diseases. Ceylon Med J 1985;30:l59-173.
Pharmacology and Therapeutics
Cutaneous Leishmaniasis Treatment with Combined Cryotherapy and Intralesional Stibogluconate Injection M. A. EL DAROUTI, M.D.,
AND S. M . AL RUBAIE, M.D.
From the Department of Dermatology, Rashid Hospital, Dubai, United Arab Emirates
ABSTfiACT: A combination of both intralesional stibogluconate injection and superficial cryotherapy (not including the base of the lesion nor the 1-2 mm rim of the surrounding normal skin) was performed in an attempt to improve the therapeutic efficacy of either of the two modalities when used separately in the treatment of cutaneous leishmaniasis. This combined therapy resulted in a 100% cure rate in 15 patients with 23 lesions of cutaneous leishmaniasis. Two control groups, one treated with superficial cryo and the other treated with intralesional stibogluconate injection alone were included in the study for evaluation. The results obtained by combined superficial freezing and intralesional stibogluconate injection were much more impressive than those obtained by each of the two modalities when used alone.
C
utaneous leishmaniasis is a specific granuloma of the skin caused by Leishmania tropica,^ and is commonly seen in tropical and subtropical areas. After an incubation period ranging from few weeks to few months it starts as a furunclelike papule that in time enlarges and frequently ulcerates and finally heals within approximately one year, leaving behind a characteristic, permanent, depressed and disfiguring
anaphylactold reaction. Headache, vomiting, fainting, arrythmias, seizures, and muscle and joint pain are common side effects of parenterally administered antimonial preparations.' Intralesional injections of pentavalent antimonials may be effective and are preferred for the localized cutaneous lesions of leishmaniasis because of fewer side effects than the parenterally administered antimonials.'' Unfortunately, when used alone complete recovery is not the rule. Cryotherapy was found useful in the treatment of localized cutaneous leishmaniasis.''^ Extensive freezing of the lesions is destructive, painful, and the damage produced by it may be slow to heal. Light freezing is better tolerated by the patient but is not equally effective. In this study, a combination of both intralesional antimonial injection and superficial freezing was tried on a group of 15 patients in an attempt to improve the efficacy of each of the two modalities when used alone. Patients and Methods Fourty-four patients, 19 women and 25 men with a mean age of 32 years, were included in this study (Table 1); tbere were 60 lesions of leisbmaniasis studied. Tbe mean duration of lesions was 9 weeks, and the mean size was 3 cm. Ulcerations were seen in 18 lesions. Eight of tbe lesions were associated witb tbe development of satellites. The most frequently affected sites were the lower limbs (28 lesions) and upper limbs (22 lesions). Tbe face was less frequently involved (8 lesions), and only two lesions were found on the back. Biopsy specimens were taken from 45 lesions. Early lesions and nonulcerated areas of ulcerated lesions were chosen for biopsy to increase tbe possibility of detecting tbe organisms. Microscopic features showed granulomas witb numerous macropbages, plasma cells, and lympboid cells. Polymorpbs and esinopbils were seen in variable numbers. Tbe causative organisms (leisbmania donovan bodies) ap-
Pentavalent antimonials such as meglumine antimonate (glucantime) or sodium stibogluconate (pentostam) still form the basis for all treatment of leishmaniasis; however, they should be used with care particularly when administered via intravenous or intramuscular routes. They tend to accumulate and are excreted slowly. They may cause cardiac, hepatic, renal, and cerebral toxicity and can precipitate an Address for correspondence: M. A. El Darouti, Department of Dermatology, Rashid Hospital, Dubai, United Arab Emirates.
56
No. 1
CUTANEOUS LEISHMANIASIS
TABLE 1. Basic and Case History Data Group 1 Number of patients Dropouts Number of cases evaluated
18
3 15
Croup 2 17 3
Croup 3 19
14
4 15
9
8
8
6
6
7
32
30.5
32.5
23 10
19
18 9.5
10
9
9
9
7
6
3 1
3 —
2 1
7
5 2
2
Sex
Men Women Age (years, mean) Number of lesions (mean) Duration (weeks, mean) Sites of lesions Legs Arms Face Back Ulceration Satellite lesions Size of lesion (cm, mean) Biopsy Organisms detected with H & E Organisms detected with Ciemsa Pretreatment Yes No
9
4 3.5 15 5 8
2.5 15 4 9
—
—
15
15
6 3 15 5
El Darouti and At Ruhaie
57
tbe cartridge dental syringe to minimize tbe pain and allow easier infiltration of tbe lesions. Tbe lesions were examined weekly for 6 weeks. Signs of improvement such as diminusion in size, healing of tbe ulceration, flattening, and fading of color were recorded. Tbe second group (14 patients witb 19 lesions) was treated witb cryotberapy alone using superficial freezing in tbe same way as tbe first group. Results of therapy were recorded every week for 6 weeks. Patients of tbe tbird group (15 patients with 18 lesions) were treated by intralesional injection of stibogluconate every otber day for 10 injections. Tbe drug was administered in tbe same way as in the first group. Signs of improvement were registered every week for 6 weeks. After fhe end of tbe treatment period (6 weeks) all groups of patients were examined every month for any signs of recurrence and for evaluation of tbe side effects sucb as depigmentation and scarring. Tbe final evaluation was done 3 montbs after conclusion of tberapy. Results were analyzed using student's t test. Results
7 — 15
peared as intracellular and extracellular circular or ovoid bodies. Leishmania donovan bodies were detected easily by bematoxylin and eosin stain in 14 of tbe specimens. Ciemsa stain was needed for tbe clarification of tbe organisms in 24 specimens. Liver and renal function tests and an ECG were assessed for all tbe patients. Ten patients were excluded from tbe study either because of abnormalities of liver and/or renal function tests (3 patients), or because of failure of compliance (7 patients). Treatment Pafienfs were divided into three groups. Patients in tbe first group (15 patients witb 23 lesions) were treated by combined cryotberapy and intralesional stibogluconate injection. Lesions were subjected to superficial freezing using liquid nitrogen probe (Spembly cryo surgery system DFS 30, Spembly Ltd, Hampsbire, England). Lubricating jelly was applied to the lesions before freezing to achieve better contact between fbe cryo probe and tbe surface of the lesion. Freezing was continued for 10 seconds only (until tbe surface turned wbite). Care was taken to avoid freezing of tbe bases of the lesions and tbe surrounding 1-2 mm of tbe normal skin. Edema and/or bullae formation always followed within 8-12 bours. Patients were instructed to apply saline compresses three times a day until a crust forms and dries up (usually 1-2 weeks). Thereafter antibiotic creams were applied to belp remove tbe crust. Freezing was repeated three times, once every 2 weeks. Intralesional stibogluconate (2-5 ml according to the size of tbe lesion) was injected every otber day. Tbe first injection was given immediately after tbe first session of cryo (following tbawing of tbe lesion) and was repeated every other day for 10 injections. Stibogluconate was injected by
The results are illustrated in Table 2. All patients of the first group, treated with combined cryo therapy and intralesional stibogluconate injection were cured after 6 weeks from the start of therapy. Nineteen lesions (82%) were cured after 4 weeks and needed no further therapy. Small and nonulcerative lesions showed a remarkably rapid response, while large, ulcerative lesions and lesions on the lower limbs took longer to heal. Healing was associated with temporary hypopigmentation in 19 lesions, ie, 82% of the cases. Darkskinned patients were more prone to this side effect. Complete repigmentation, which started with perifollicular darkening, occurred in 8-12 weeks. Minimal scarring was present at the site of 30% (7) of the lesions; all such lesions were ulcerative. In the second group (treated with cryo alone) 11 patients, with 13 lesions (68% of the patients) were completely cured by the end of the 6th week, ie, 2 weeks after the last cryo session. As in the first group, small and nonulcerated lesions responded better to treatment. Lesions on the lower limbs responded more slowly than lesions elsewhere. Temporary depigmentation occurred at the site of 16 (84%) of the lesions. Nonetheless, complete repigmentation was evident after 3 months. Minimal scarring occurred in six (31%) of the lesions; it was seen more frequently in association with ulceration. In the third group, treated with intralesional pentostam injection alone, only six patients (with eight lesions) were cured. The cure rate was 44%. There were no systemic side effects to the intralesional injection of stibogluconate. Scarring occurred in
58
INTERNATIONAL JOURNAL OE DERMATOLOGY TABLE 2.
Number of Patients Number of lesions Treatment
Healing After 4 weeks After 6 weeks Side effects Reversible hypopigmentation Scarring E.C.G. Liver or renal abnormalities
January-February 1990
Vol. 29
Results of Treatment of Leishmaniasis with Comhined Cryo and Intralesional Stihogluconate Injection and with either Modalities Civen Alone Group 1
Group 2
Group 3
15 23 Combined superficial cryotherapy and intralesional pentostam injections
14 19 Superficial cryotherapy
15 18 Intralesional stibogluconate injection
19 (82%) 23 (100%)
10(52%) 13 (68"/o)
6 (33%) 8 (44%)
19 (82%) 7 (30%)
16 (84'y()) 6 (31%)
10(55%)
ten (55%) of the lesions and was more commonly seen at the sites of ulcerations. The overall results showed clearly that the combined freezing and intralesional stibogluconate injection was superior to either cryotherapy or intralesional stibogluconate injection when given separately. The difference in results were statistically significant (p
Discussion
Despite the introduction of many drugs in the treatment of leishmaniasis such as ketoconazole,^ dapson,^''' rifampicin and antimalarials,^ pentavalent antimonials are still the most widely used drugs. The parenteral administration of pentavalent antimonials, however, may be associated with side effects such as electrocardiographic changes (depressed T wave and conduction defects), transaminase rise, and acute renal insufficiency." Nevertheless, these complications usually are not encountered if the drugs are given intralesionally. One course of intralesional injections may not be sufficient and more than one course will be needed. In this study intralesional injection of stibogluconate was effective only in 44% of the cases when it was used alone. This result, however, reached 100% when intralesional stibogluconate injection was combined with freezing; a second course was never required. The increased efficacy of intralesional antimonial injections when it was combined with freezing could be attributed to either a synergistic effect of both lines of therapy or, alternatively, to the possibility that cryo, causing disturbances in the wall permiability"* of the macrophages harboring the organisms, results in a
better accessability of the antimonials inside the macrophages where the concentration of leishmania donovan bodies is maximum. Deep freezing of the leishmania lesions, ie, until the whole lesion and a 1-2 mm margin around it is frozen'"'" is probably not necessary, as deep freezing is not devoid of side effects.'^ The edema and/or bullous lesions that follow deep freezing usually take a long time to heal and may result in the formation of unsightly scarring. Moreover, permanent depigmentation, particularly in patients with dark complexions, is more commonly seen after deep freezing. Deep freezing in certain localities, such as over the shins, is better avoided. We have found light freezing in the treatment of leishmaniasis to be equally effective and not associated with the side effects that would occur with the use of deep freezing. Healing time and depigmentation after light freezing, in our experience, took a remarkably shorter time than that required for the lesions produced by deep cryo, and scarring was absent or minimal. The combination of both light cryotherapy and intralesional injection of pentavalent antimonials is more effective in the treatment of cutaneous leishmaniasis than either cryotherapy or intralesional antimonial injections when used alone. It can be considered a highly effective and safe approach for the treatment of cutaneous leishmaniasis. References 1. Farah ES. Protozoan and Helminth infections. In: Fitzpatrick TB, Eisen AZ, Wolff K, et al, eds. Dermatology in general medicine. 3rd ed. New York: McGraw-Hill, 1987:2477-2507. 2. Harman RR. Parasitic worms and protozoa. In: Rook A, Wilkin-
No. 1
3. 4.
5. 6.
7.
CUTANEOUS LEISHMANIASIS
son, DS, Ebling FJ, et al, eds. Text book of dermatology. 4th ed. Oxford: Blackweli Scientific Publications, 1986:9871031. Moschella SL. Diseases of the mononuclear phagocytic system. In: Moschella SL, Hurley HJ, eds. Dermatology 2nd ed. Philadelphia: WB Saunders, 1985:890-1000. Oliveira Neto .MW, Pirmez C, Coutinho S, et al. Interleslonal pentavalent antimonial therapy in American cutaneous leishmaniasis: a two-year follow-up study. Presented at 17th world congress of dermatology. Berlin: World Congress of Dermatology, 1987. Jolliffe DS. Cutaneous leishmaniasis from Brazile: treatment with ketoconazole. Clin Exp Dermatol. 1986,11:62-68. Dogra JB, Misra NS. Cutaneous leishmaniasis: therapeutic efficacy of dapson in the commonly existing subtypes. Presented at 1 7th world congress of dermatology. Berlin: World Congress of Dermatology, 1987. Jaideep D, Bhupender BL, Shayam NM. Dapson in treatment of cutaneous leishmaniasis. Int J Dermatol. 1986;25:398-400.
El Darouti and A! Rubaie
59
8. Marsden PD. Leishmaniasis cutaneous and mucocutaneous. In: Maddin S, ed. Current dermatologic therapy. Philadelphia: WB Saunders, 1982:268-272. 9. Zacadan SA. Cryogenics: the cryolesion and the pathogenesis of cryonecrosis. In: Zacarian SA, ed. Cryosurgery for skin cancer and cutaneous disorders. St. Louis: C.V. Mosby, 1985:1-31. 10. El Banhawi MO, El Tonsy MH, George WM. Cryosurgery in treatment of cutaneous leishmaniasis. Presented at the 17th World Congress of Dermatology. Berlin: World Congress of Dermatology, 1987. n . Leibovici V, Aram H. Cryotherapy in acute cutaneous leishmaniasis. Intj Dermatol. 1986;25:473-475. 12. Zacarian SA. Complications, indications, and contraindications in cryosurgery. In: Zacarian SA, ed. Cryosurgery for skin cancer and cutaneous disorders. St. Louis: C.V. Mosby, 1985:283-298.
Ayurvedic Dermatology On the subject of leprosy, a well-written book entitled "A Therapeutic Guide to Ayurvedic Medicine", written in 1970 by Pandit R. R. Pathak of India, who was once the Director of the Ayurvedic Research Institute at Navlnna, near Colombo, merits attention. This book is based on ancient Sanskrit ayurvedic texts. In the 25 page chapter on skin diseases or Tvak-vikara he lists about 36 diseases which can be recognized as specific diagnoses. Actiologically, all diseases were considered to be a result of disturbance in the 3 bodily humours which were Vatha or wind, Pitha or bile and Sema or Phlegm. It may seem that these 3 humours are identical with what one normally conceives when these terms are used. For example, "wind" in relation to human physiology would bring to mind such ideas as belching or flatus or even gurgling in the abdomen; "bile" makes us think of nausea or bilious vomiting; and "phlegm" implies a cold or cough with abundant sputum or saliva. However, it is important to realize that though these common terms have been used, the ayurvedic concept of the 3 humours cannot be subject to such simplistic interpretation. All skin disorders were divided into Major and Minor categories. The ancients recognized 7 major skin diseases and 11 minor disorders. On a basis of derangement of the humours, all skin disorders were believed to be a result of fault in one, two or all three of the humours. Thus they concluded that there were 7 aetiological bases for these diseases. The commonest of the 36 skin disorders was eczema. It is noteworthy that tinea versicolor or alu hang (literally "grey skin") was not considered a skin disease, but was admired as providential embellishment termed gomara. Terms to describe clinical features and the appearances of lesions were rather limited but constituted the basis of modern clinical dermatology. The macule and papule, and features such as weeping and dry, were described. On the prophylactic aspect the ancients believed that there were medicines which improved the health of the skin and made it resistant to disease. From the therapeutic viewpoint the basic principle was that the causative humour too must be treated in addition to its manifestations. Among the large number of herbal and other preparations used were several which are recognized as being at least kind to the skin. Many of us have seen or heard of the Kustarajagala in Weligama. It is a granite statue which stands between 88th and 89th mile-posts on the old highway to Galle. Several versions have been written to explain its history and significance since Bennett gave a long account of it in 1843. Kustaraja has been literally translated to mean 'leper king'. As already mentioned the ancients included leprosy among the seven Maha-kushtas, and as to the disease in any particular instance having been leprosy itself is anybody's guess.—Ranasinghe L: Mussings relating to skin diseases. Ceylon Med J 1985;30:l59-173.
