ARTICLE
Cutaneous leishmaniasis(CL) is a disease of antiquity [1] and known to
the old world since, at least, the first century AD. Its enormous ecological
diversity has resulted in difficulties controlling the disease. Neither
sandfly control nor the control of the reservoir are easy to apply and
both approaches are expensive and unaffordable by most of the developing
countries. In addition, treatment failure, emerging drug resistance and
relapse are some of the commonly encountered distressing problems in the
management of CL and its erysipeloid variety is no exception [2, 3].
Erysipeloid CL is a very rare and somewhat obscure manifestation of Old
World cutaneous leishmaniasis which has been reported almost entirely
from Iran [2, 3].
Although it involves the nose and cheeks of middle aged to elderly females,
however, not every elderly female with cutaneous leishmaniasis manifests
this type of presentation.
The reasons behind this peculiar age and sex predilection and geographical
distribution is not really clear. The exact natural history of the disease
is not known either, since the entity is quite infrequent and only seen
sporadically. However both acute and chronic forms of the disease have
been reported [2, 3]. There is, albeit unfortunately, no one novel drug
for treatment of CL. However treatment has primarily been dependent on
the antimonials which have remained the first line drugs for about half
a century [4]. In addition, these drugs are expensive and occasionally
associated with serious side effects [5].
Here we have presented our experience with the use of a new therapeutic
modality, a topical herbal extract of pure natural source namely "Z-HE"
[6-8], for those patients with erysipeloid cutaneous leishmaniasis (ECL).
Patients and Methods
Patients
Over the last few years, 14 consecutive cases with erysipeloid-type
of CL were encountered. All cases had a clinical interview and underwent
a thorough physical examination after giving written consent for participation
in the study. The size of the lesion and the degree of erythema were clinically
assessed during the first visit and thereafter during each clinical follow
up. This was complemented by initial and subsequent photographs of the
lesions too.
Diagnosis
The diagnosis of the disease was based on the clinical presentation, the
presence of typical facial appearance with an infiltrative butterfly-like
erythematous plaque involving the cheeks and nose and the presence of
amastigotes in the skin smears and/or biopsy specimens of the lesions.
Treatment
Except for patient no 3, all the patients had received varying
numbers of meglumine antimoniate injections,
albeit unsatisfactorily, in the past. However, none had received any therapy
over the last 2 months prior to their enrollment in this study.
All cases were treated with a freshly prepared paste of our herbal extract
Z-HE which consists of a mixture of Althaea officinalis, Althaea rosa
and members of the family Leguminosa faliacaea, Malvacaea and Lythracaea.
The paste was applied over the lesion and was covered by a dressing which
was changed every 24 hrs. The same procedure was done for 5 consecutive
days, and thereafter every 2 weeks, as needed, for a maximum period
of 3 months.
Paraclinical investigations
Complete blood counts, serum creatinine, blood urea nitrogen, and liver
function studies, were carried out on the patients. The same parameters
were rechecked during the treatment and at 3 and 6 months of
the clinical follow up of the patients too. Parasitologic studies were
done every 2 weeks until getting negative.
Follow up
All the patients were regularly followed up for more than a year, after
the termination of therapy, and were rechecked for signs of improvement
or cure. Cure was defined as complete healing and re-epithelialization
of the lesion with a negative skin smear or biopsy for amastigotes and
no relapse for a period of 12 months after termination of a successful
therapy.
In addition, the patients were classified into acute and chronic groups
(each 7 patients) and were compared in terms of their clinical response
to therapy, duration of follow up and relapse of the disease. Those with
a disease duration of less than 12 months were labeled as acute and
patients with longer duration were categorized as being chronic.
Results
Of our 14 cases, there were 13 females and 1 male, with
an age range of 40 to 70 years (mean = 59 years).
Most of the patients had a sharply demarcated erythematous, scaly butterfly-like
lesion over the mid face (Fig.
1a).There was, however, no lymph-adenopathy. The duration of the disease
ranged from 1 to 84 months (mean = 30 months).
It was 1 to 8 months (5.5 ± 2.4) in the acute group
and 12 to 84 months (50 ± 30) in the chronic group
(Table I). Direct smear
and/or biopsy from the lesions were positive for the presence of amastigotes
in every case.
Unfortunately 2 cases were lost to follow up. Eleven (92%) of the
remaining12 patients had evidence of complete re-epithelialization
and healing in a matter of 1 to 7 months (mean = 4.0)
and had no relapse after 12 months of follow up. Although the remaining
patient had an initial satisfactory response to therapy, she had a subsequent
relapse (Table I). Histopathologic
studies in 10 patients (2 cases rejected the procedure), showed
disappearance of amastigotes within 2 weeks to 5 months (mean =
2.6 months) after the therapy.
Except for the duration of the disease, there was no significant difference
between the acute and chronic cases and complete recovery was equally
distributed among the either group. The mean follow up period was 52 months
during which one patient (8%) had evidence of relapse. No scar was left
behind in any of the patients (Fig. 1b).
Drug-induced complications
No drug associated morbidity was noted during the entire period of clinical
trial and follow up. All hematologic, renal and hepatic parameters remained
normal throughout the same periods as well.
Discussion
The lesions of localized CL usually heal within 6-12 months, and
leave a scar behind [9]. The immunity is not complete in every case and
10% of patients may develop a second infection with the same zymodeme
of Leishmania [10]. Generally speaking, treatment should be confined
to the most severe forms of disease, especially if the lesions are located
on cosmetically important areas like the face, to reduce the size of the
resultant scar [9]. Chemotherapy has remained the cornerstone of therapy
for CL in most endemic regions of the world. However the available drugs
are few and their efficacy varies from one country to another. Sodium
stibogluconate (Pentostam®) and meglumine antimoniate (Glucantime®), have
remained the mainstay of therapy for the past few decades [4, 5, 9]. These
drugs, however, are quite expensive and their side effects are frequent,
especially when used for more than 20 days [11, 12]. Treatment of
CL with antimonials poses another important problem due to variation in
species sensitivity [13] and there is increasing concern regarding the
recently reported emergence of resistance to these drugs in many countries
[14, 16].
Actually, all except one of our cases, had previously been treated with
glucantime with no satisfactory results and 7 patients had developed
a chronic and persistant disease. Although the underlying reasons for
such geographic variability are not fully clear, however the interaction
between the mammalian host, the parasite and the vector are most probably
different in one area from the others. Generalizations, therefore, are
quite difficult and WHO has identified each major ecological type of disease
as a nosogeographic entity [17].
Other chemotherapeutic agents such as allopurinol [18, 19] and interferon-gamma
[5, 9, 20] have recently been used too. Their success rate, however, has
been variable and the high cost of the latter poses a major limitation
to its use.
Although the use of intra-lesional injections of antimonials has been
reported to have a success rate of 72-76 percent [5, 21], however
it requires frequent painful injections of each individual lesion which
makes it impractical in those with multiple lesions or in cases with erysipeloid
CL with a large area of strategic involvement over the nose and cheeks.
The administration of topical paromomycin- containing preparations has
also been reported. El-On et al., found a faster clinical response
in their treated patients with CL than the untreated ones [22]. The efficacy
of 10% paramomycin-containing formulations, however, was no better than
placebo for treatment of Old World CL in Iran [23] and Tunisia [24]. In
addition their use has been associated with some untoward reactions [25].
As such, therefore, the need for a readily available, cheap, non-toxic,
topical easy to apply and more effective drug for the treatment of CL
is quite clear.
Cutaneous leishmaniasis is quite frequent in our area [2, 6-8, 17] and
erysipeloid type lesions are one of its very rare and unusual manifestations
which have been only reported from Iran [2, 3] and Pakistan [26]. It typically
involves the mid-face areas (nose and cheeks) of middle-aged females and
may become disfiguring and troublesome especially if it becomes chronic.
Eleven (92%) out of our 12 cases had a complete cure, with no subsequent
relapse, indicating the remarkable therapeutic effect of Z-HE in these
patients, both the acute and chronic ones. Z-HE is a pure herbal mixture
which has already been proved to be superior to Glucantime® in the treatment
of patients with acute and chronic CL [6-8] and to be free of the toxic
effects seen with the use of antimonials [5, 9, 11, 12]. None of our cases
developed any drug-related toxicity and all the paraclinical investigations
remained normal throughout the study period.
CONCLUSION
Although the active ingredient(s) and the mechanism(s) of action of Z-HE
are currently not known, its ease of preparation, topical application, lack
of side effects, low cost and its satisfactory cosmetic effects make it
a promising drug for use in the treatment of lesions of CL, especially the
quite strategically located ones. Further controlled studies, however, are
needed to establish which of the currently available topical therapeutic
agents is the most effective one in the treatment of lesions of the old
world cutaneous leishmaniasis.
We would like to acknowledge Mr. Ebrahim Zerehsaz for his excellent
work in preparing the herbs, dressing the patients and photographing the
lesions, Mr. HR Tabatabaee for his assistance in statistical analysis,
Mrs A Bamia for her secretarial work, and Mr. Shahab Rezaian whose assistance
made this work possible.
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