Intermediate/borderline disseminated cutaneous leishmaniasis

Leishmaniasis is a diverse group of vector‐borne diseases caused by a subset of predominantly intracellular protozoal species of the genus Leishmania. Cutaneous disease may be subdivided into localized, intermediate, and diffuse forms. Intermediate cutaneous leishmaniasis is distributed widely in Latin America and is characterized by cutaneous lesions, which may be accompanied by mucosal disease and demonstrate a tendency toward chronicity and relapse as well as resistance to standard treatment regimens. Leishmania parasites of the subgenus Viannia have been identified as the major etiologic agent of this subset of infections. The present review provides a brief perspective on leishmaniasis followed by a review of classification, transmission, clinical presentation, and evolution of disease, immunology, and current treatment approaches for the intermediate/borderline disseminated subset of cutaneous leishmaniasis.     

Leishmaniasis cutánea y mucocutánea

Leishmaniasis is a chronic disease caused by flagellate protozoa of the genus Leishmania. It is a global disease, but most cases are seen in South America, the Mediterranean, and some areas of Asia and Africa. The 3 main types of leishmaniasis are cutaneous (the most common), mucocutaneous, and visceral (the most severe). Visceral leishmaniasis is also known as kala-azar. Leishmaniasis is diagnosed by demonstrating the presence of Leishmania amastigotes in clinical specimens using direct microscopic examination or molecular analysis. Various treatments exist, although the evidence supporting the options available for cutaneous leishmaniasis is weak. Both the classical presentation of leishmaniasis and our management of the disease have changed in recent decades because of acquired immune deficiency caused by conditions such as HIV infection or the use of TNF inhibitors.     

A Preliminary Study Aimed at the Detection of Leishmania Parasites in Subjects with Cutaneous Leishmaniasis Using Polymerase Chain Reaction

As a basic study for future diagnosis of cutaneous leishmaniasis, we tried to detect Leishmania parasites representing different species in the subgenera Leishmania and Viannia from subject patients with cutaneous leishmaniasis by using the polymerase chain reaction (PCR) with the subgenus Viannia specific primer. Four out of the 14 specimens revealed an amplified DNA of 70 bp specific for the subgenus Viannia (L. braziliensis comples). No bands were detected in the rest of the specimens belonging to the subgenus Leishmania and unclassified groups. The base sequences of the amplified DNA corresponded with those of the L. (V). braziliensis kinetoplast minicircle. We concluded that PCR using the present primer specific for the subgenus Viannia would be useful in detecting Leishmania parasites in lesions of cutaneous leishmaniasis caused by the L. braziliensis complex.     

New World Cutaneous Leishmaniasis Treated with Intralesional Injection of Pentavalent Antimony

Cutaneous leishmaniasis is a skin infection caused by the Leishmania species, an intracellular protozoan parasite that is transmitted by various species of female sandflies. According to the geographic distribution and vectors, leishmaniasis is classified as Old World or New World cutaneous leishmaniasis. In Korea, 24 cases of Old World cutaneous leishmaniasis have been reported, but New World cutaneous leishmaniasis has not been reported as yet. A 37-year-old man presented with a 3-month history of a painful and erythematous nodule with two satellite papules on the left postauricular area and a papule on the left arm after traveling to the Amazon region in Brazil. After we performed skin biopsies of the lesions, diagnosis of cutaneous leishmaniasis was made by the histopathological findings. After intralesional injection of sodium stibogluconate (Pentostam®, GlaxoSmithKline) twice a week for 4 weeks, the lesions improved with scarring. Herein, we discuss this case of New World cutaneous leishmaniasis that was successfully treated with intralesional injection of sodium stibogluconate (Pentostam®) in Korea.     

An imported case of cutaneous leishmaniasis caused by Leishmania (Leishmania) donovani in Japan

Leishmaniasis is a major world health problem, and 12 million people are estimated to be infected in 88 countries. There have been few reports of leishmaniasis in Japan and all were of foreign origin; therefore diagnosis is difficult for Japanese physicians. There are 21 different pathogenic Leishmania species, and identification is obtained by polymerase chain reaction (PCR). Here we report an imported case of leishmaniasis by Leishmania (Leishmania) donovani infection from Sri Lanka. L. (L.) donovani usually causes visceral leishmaniasis, but in this case, the patient manifested cutaneous leishmaniasis. The identification of Leishmania species by PCR and investigation of the patient's background such as nationality and disease endemicity are important for diagnosis and treatment. This is the first report of cutaneous leishmaniasis by L. (L.) donovani in Japan.     

VALUE OF TOUCH PREPARATIONS (IMPRINTS) FOR DIAGNOSIS OF CUTANEOUS LEISHMANIASIS

Background. The clinical diagnosis of cutaneous leishmaniasis is confirmed by demonstrating the organism on a superficial smear or on a biopsy of the lesion. Misdiagnosis in a biopsy specimen may be due to scanty Leishmania organisms that may not be identified in histologic sections. Methods. Punch biopsies of skin lesions, suspected clinically to be cutaneous leishmaniasis, from 29 patients were taken. Touch smears on slides were air-dried, fixed with methyl alcohol, and stained with Giemsa stain. Results of routine histologic examination were then compared with those of touch preparation. Results. Twenty-one cases were positive for leishmaniasis. In 18 cases, the organisms were seen both in the biopsy and in the touch preparation. In three cases, the organisms were only identified on touch preparation. Conclusions. A touch preparation improves the sensitivity of the diagnosis of cutaneous leishmaniasis without incurring additional cost to the laboratory.     

Cutaneous presentation of disseminated histoplasmosis as a solitary peri‐anal ulcer. Case report and discussion

Disseminated histoplasmosis has a diverse and non‐specific range of clinical signs and symptoms. In a significant minority of patients, cutaneous lesions are apparent at the time of initial presentation, affording an opportunity to establish the diagnosis from a skin biopsy. The most frequently reported clinical scenario in immunocompromised patients with cutaneous involvement is that of multiple papulo‐nodular lesions on the face, trunk or extremities. The following report features an immunocompetent patient who presented with a solitary ulcerated plaque on the buttocks close to the anal verge. This case presentation underscores the broad spectrum of clinical presentations as well as the potential for diagnostic confusion with protozoa such as Leishmania or Trypanosoma species during histopathologic examination if special stains for fungal organisms are not performed.     

Disseminated cutaneous Mycobacterium kansasii infection presenting with Rosai–Dorfman disease‐like histological features in a patient carrying anti‐interferon‐γ autoantibodies

Typical cutaneous non‐tuberculous mycobacteria (NTM) infections show a histopathology pattern of granulomas with admixed Langhans giant cells, and abscesses may be observed in acute lesions. Herein, we describe a patient carrying a high titer of autoantibodies to interferon (IFN)‐γ with disseminated Mycobacterium kansasii infection presenting with emperipolesis and Rosai–Dorfman disease (RDD)‐like histopathological features characterized by remarkable, large, pale‐staining “RD cells”, which were CD68 and S100 positive and CD1a negative. The patient was misdiagnosed with RDD initially, but exhibited a poor response to all interventions. A re‐biopsy revealed Langhans‐type multinucleated giant cells; multiple definite acid‐fast bacilli were also found. M. kansasii was isolated from cultured tissues. Anti‐NTM treatment was initiated. After treatment, all lesions resolved almost completely within the following month. High‐titer anti‐IFN‐γ autoantibodies were detected during follow up, leading to the diagnosis of adult‐onset immunodeficiency syndrome. In conclusion, patients carrying high‐titer autoantibodies to IFN‐γ who also have a disseminated cutaneous M. kansasii infection may present with RDD‐like histopathological features, which may be a pitfall in the diagnosis of disseminated cutaneous NTM infections.     

Visceral leishmaniasis with cutaneous symptoms in a patient treated with infliximab followed by fatal consequences

Leishmaniasis is an infectious disease caused by parasitic flagellates of the genus Leishmania. The authors present a case of 44‐year‐old man with Crohn's disease treated successfully with infliximab. This case report shows rare visceral leishmaniasis with cutaneous symptoms in an immunocompromised patient. Skin manifestations may occur before or after the visceral infection and they are often diverse.     

Identification of Leishmania species by high-resolution DNA dissociation in cases of American cutaneous leishmaniasis

BackgroundAmerican cutaneous leishmaniasis is an infectious dermatosis caused by protozoa of the genus Leishmania, which comprises a broad spectrum of clinical manifestations depending on the parasite species involved in the infections and the immunogenetic response of the host. The use of techniques for amplification of the parasites DNA based on polymerase chain reaction polymerase chain reaction and the recent application of combined techniques, such as high-resolution DNA dissociation, have been described as a viable alternative for the detection and identification of Leishmania spp. in biological samples.ObjectivesTo identify the Leishmania species using the polymerase chain reaction high-resolution DNA dissociation technique in skin biopsies of hospital-treated patients, and compare with results obtained by other molecular identification techniques.MethodsA retrospective study assessing patients with suspected American cutaneous leishmaniasis seen at a hospital in São Paulo/Brazil was conducted. The paraffin blocks of 22 patients were analyzed by polymerase chain reaction high-resolution DNA dissociation to confirm the diagnosis and identify the species.ResultsOf the 22 patients with suspected American cutaneous leishmaniasis, the parasite was identified in 14, comprising five cases (35.6%) of infection by L. amazonensis, four (28.5%) by L. braziliensis, two (14.4%) by L. amazonensis + L. infantum chagasi, two (14.4%) by L. guyanensis, and one (7.1%) by Leishmania infantum chagasi. In one of the samples, in which the presence of amastigotes was confirmed on histopathological examination, the polymerase chain reaction high-resolution DNA dissociation technique failed to detect the DNA of the parasite.Study limitationsThe retrospective nature of the study and small number of patients.ConclusionsThe method detected and identified Leishmania species in paraffin-embedded skin biopsies with a sensitivity of 96.4% and could be routinely used in the public health system.     

Cutaneous Leishmaniasis from Belize–treatment with ketoconazole

Eight patients suffering from cutaneous leishmaniasis acquired in Belize were treated with 800 mg oral ketoconazole daily for 28 days. Four were infected with Leishmania mexicana mexicana and four with Leishmania braziliensis brazitiensis. On completion of therapy, all cases of Leishmania mexicana mexicana infection and one of Leishtaania braziliensis braziliensis infection showed significant clinical improvement. Clearance of infection was confirmed by the absence of amastigotes in post-treatment biopsy specimens and negative post-treatment cultures. The possibility of spontaneous clinical healing of these ulcers within such a short period of time is discussed but considered most unlikely. No side-effects were observed during this study which suggests that ketoconazole might be a safe and effective form of therapy for cutaneous leishmaniasis caused by Leishmania mexicana mexicana.     

Mucosal and mucocutaneous leishmaniasis in Iran from 1968 to 2018: a narrative review of clinical features,treatments, and outcomes

Leishmaniases are worldwide zoonotic infectious diseases caused by different types of intracellular protozoan species of the genus Leishmania. Leishmaniasis as an important vector-borne parasitic disease is transmitted between mammalian hosts by female sandflies. There are three main clinical forms of disease with varied severity: visceral leishmaniasis (VL), cutaneous leishmaniasis (CL), and mucocutaneous leishmaniasis (MCL). MCL is the most uncommon form of this syndrome in the Old World. Accordingly, the reports have characterized that patients with the involvement of mucous membranes are rare even in endemic areas. It is well-known that MCL is a rare clinical manifestation in Iran, but there have been several different cases of patients with mucosal (ML) or MCL in some parts of Iran during the past 50 years. Therefore, we aimed to report and present clinical and epidemiological features of ML or MCL in different regions of the country. Also, we demonstrated specified Leishmania species causing the ML in some cases. The present narrative review indicates that ML or MCL is not unexpected in Iran. Based on the findings of the recent studies, it is concluded that diagnosis of ML should be considered by physicians in Iran.     

A pilot study comparing low‐dose liposomal amphotericin B with N‐methyl glucamine for the treatment of American cutaneous leishmaniasis

Background Cutaneous leishmaniasis is an infectious re‐emerging disease that has increased in incidence worldwide. Antimony, a highly toxic drug, remains the first choice therapy to treat it. Liposomal amphotericin B is active against Leishmania and is less toxic than antimony. Objective To compare low‐dose liposomal amphotericin B with N‐methyl glucamine for the treatment of American cutaneous leishmaniasis. Patients/Methods In a controlled open‐label trial 35 patients with a localized form of American cutaneous leishmaniasis were included. They were allocated to a first group treated with 1.5 mg/kg/day of liposomal amphotericin B for 5 days, or to a second one treated with 20 mgSbV/kg/day of N‐methyl glucamine for 20 days. Results In the first group, 50% and 81% of patients experienced a clinical cure and clinical improvement respectively. There was a 100% clinical cure in the second group. Conclusion Liposomal amphotericin B seems to be promising and safe for the treatment of American cutaneous leishmaniasis.     

A new scenario in the immunohistochemical diagnosis of cutaneous leishmaniasis

Cutaneous lesions of leishmaniasis are easy to diagnose when clinically obvious or when amastigotes are numerous in the biopsy. However, this is not always the case. In difficult cases, the diagnosis of leishmaniasis requires a reliable tool to identify the microorganisms. The identification of the parasite via microscope has a superior sensitivity to that of culture, and molecular techniques, such as polymerase chain reaction (PCR), highly improve the sensitivity of the diagnosis. Alternatively, immunohistochemistry has emerged as an affordable alternative to PCR. Several laboratories have produced their own antibodies against Leishmania and seem satisfied with the results. Nevertheless, most of these antibodies are not commercialized or standardized. Pathology also welcomed the unexpected positivity of amastigotes with certain clones of anti‐CD1a. The latter does not universally stain all species of Leishmania, with a low sensitivity for New World species. In conclusion, although anti‐CD1a is a reliable complementary tool in the diagnosis of leishmaniasis, pathologists should familiarize themselves with one of the specific antibodies against Leishmania and globalize its use, standardizing and adapting the technique.     

Cutaneous leishmaniasis in a child treated with oral fluconazole

We report a case of cutaneous leishmaniasis in a 3‐year‐old West African girl with a 3‐month history of multiple disfiguring, infiltrated, ulcerating and variably necrotic granulomatous plaques on the limbs and face that occurred after swimming in a river approximately 6 weeks before arriving in Australia. A diagnosis of cutaneous leishmaniasis, a protozoal zoonosis usually transmitted by the Phlebotomus species of sandfly, was considered. The clinico‐pathological features were consistent with Leishmania major infection, known to be the major endemic species causing cutaneous leishmaniasis in the country of origin. Because of the presence of lesions on the face, active treatment was instituted. Continuing resolution of all lesions over 6 weeks was noted to occur with cribiform scarring with the use of oral fluconazole 150 mg daily. Oral fluconazole appears to be emerging as a therapy for uncomplicated cutaneous leishmaniasis, with advantages particularly important in paediatrics.     

Treatment of imported New World cutaneous leishmaniasis in Germany

Background  Cutaneous leishmaniasis (CL), a parasitic disease which represents a public health problem, particularly in Central and South America, has become a leading condition in travelers who return from tropical countries with skin disorders. Cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis, the most common causative agent, requires systemic treatment because it is potentially able to disseminate and to cause mucosal or mucocutaneous disease. Although several drugs are available for the systemic treatment of leishmaniases, a definitive treatment regimen for infection caused by species of the Viannia subgenus has yet to be established in many countries, including Germany. Methods  We analyzed treatment outcomes in 23 returnees from Central and South America who were diagnosed with L. (V.) braziliensis CL by polymerase chain reaction. Results  Complete cure within one month following treatment was observed in 18 patients (78%). Cure was achieved with liposomal amphotericin B in 11 of 13 patients, miltefosine in five of eight patients, and meglumine antimoniate in two (of two) patients. Of the five patients (22%) who failed to respond to initial therapy, four were cured with meglumine antimoniate and one with liposomal amphotericin B. Conclusions  In this outcome evaluation of treatment of imported L. (V.) braziliensis infections, liposomal amphotericin B, miltefosine, and meglumine antimoniate proved to be effective. Conventional meglumine antimoniate showed high efficacy as a first‐line treatment and cured lesions that failed to respond to the other two drugs. A multi‐country study using standardized treatment protocols is needed to establish a definitive regimen.     

Topical glyceryl trinitrate: a possible treatment for cutaneous leishmaniasis

The treatment of cutaneous leishmaniasis (CL) is difficult in both the old and new worlds. However, nitric oxide (NO) is involved in host cell mediated immune responses against intracellular parasites such as Leish-mania major, and both in vitro and in vivo immunological studies indicate that Leishmania parasite killing- by macrophages is mediated by this substance. Glyceryl trinitrate (GTN) is an exogenous NO donor; we have successfully treated a young man with cutaneous leishmaniasis with topical GTN. We believe this to be the first reported use of GTN in the treatment of human CL. Cutancous leishmaniasis (CL) is prevalent in the Middle East and poses a difficult therapeutic problem.¹ GTN is known to be an exogenous donor of nitric oxide (NO).² Previous studies have indicated that the killing of Leishmania parasites by macrophages is mediated by NO.^3–5 We have therefore treated a young man with CI. with topical GTN.     

INTRALESIONAL TREATMENT OF CUTANEOUS LEISHMANIASIS WITH SODIUM STIBOGLUCONATE ANTIMONY

Background. Cutaneous leishmaniasis represents a difficult disease to manage in endemic areas. Systemic treatment is hampered by both expense and compliance. Side effects may play a major role in this aspect as well. Methods. The effectiveness of intralesional treatment of leishmaniasis was investigated. Seven hundred and ten patients were treated with injections of sodium stibogluconate intralesionally. The clinical diagnosis was confirmed by demonstrating the parasite in the smears obtained from the lesion. Fine insulin needle was used to infiltrate the lesion with sodium stibogluconate (0.5 to 1.0 ml). Results. Generally eight injections were sufficient, but some of the complicated lesions needed up to 24 injections. Sixty-two percent of patients were men. The majority of the study population (64%) were children below 15 years of age. The results showed that 72% of lesions healed completely, 23.9% showed some improvement, while 4.1% showed some deterioration. Lesions of the lips, cheeks, chin, and neck healed faster than lesions in other parts of the body. Side effects were mild and limited to pain at the site of the injection and hyperpigmentation in those who were treated by folk medicine. Conclusions. Intralesional treatment is as effective as the standard systemic antimonials. It offers a less expensive alternative and a low side effects profile. Our findings confirmed the findings of earlier workers. It is recommended for treatment of cutaneous leishmaniasis in endemic areas.     

Acute immobilization stress induces clinical and neuroimmunological alterations in experimental murine cutaneous leishmaniasis

Background The skin is an important component of the neuroendocrine‐immune axis. Several studies have shown that stress exacerbates skin disorders, affecting the function of sebaceous glands, keratinocytes, epidermal Langerhans cells and other cells, having an impact on the pathogenesis of many immunologically associated skin diseases. In American cutaneous leishmaniasis, we have shown the importance of the epidermis as a regulatory site, with the key participation of Langerhans cells. Objectives To analyse the effect of acute immobilization stress on Langerhans cells, substance P (SP), calcitonin gene‐related peptide (CGRP) and the natural course of infection in a murine model of cutaneous leishmaniasis. Methods BALB/c mice, susceptible to Leishmania infection, were placed under acute stress by immobilization (confinement) for 2 or 8 h before inoculation with L. mexicana (MHOM/BZ/82/BEL21). An avidin–biotin immunoperoxidase technique was used for cell and neuropeptide identification. Results The stressed animals became more susceptible to the parasite infection, which was manifested by acceleration and exacerbation of the lesions. In addition, the stressed animals showed morphological alterations (spherical bodies and shortened dendrites) and decreased numbers of epidermal Langerhans cells, when compared with control L. mexicana‐infected mice. Mice stressed for 8 h showed greater and antidromic immunoreactivity to CGRP and SP at the time of infection. Moreover, the single inoculation of parasites caused a decrease of CGRP innervation. Conclusions Acute immobilization stress induces an immunosuppressive state that further favours Leishmania invasion in susceptible animals.     

Mycobacterium abscessus Hand‐and‐Foot Disease in Children: Rare or Emerging Disease?

Mycobacterium abscessus is emerging as an important cause of cutaneous infections in sporadic cases and outbreak settings. Although immunosuppressed or elderly patients are most commonly affected, in 2006 an outbreak of clinically distinct cutaneous lesions on the hands and feet caused by M. abscessus in a population of healthy children using a public swimming pool was reported. This article describes an outbreak of skin infection in a population of healthy Italian children attending the same school and using the same swimming pool. In January 2010 we identified three children with multiple, painful nodules on the palms and soles. M. abscessus was isolated from one child's lesions. A public health investigation was conducted and a team of dermatologists and public health officers visited all of the children; 514 children were screened and 29 cases were identified overall. All of the affected children had used the school's swimming pool. These children were treated with oral clarithromycin for 4 to 8 weeks. Because of the long period of time between the presentation and diagnosis of the first cases, the possibility that the number of cases may have been underestimated cannot be excluded. To our knowledge, this is the second largest reported cluster of M. abscessus skin infection suspected to be related to swimming pool exposure in a population of otherwise healthy children. It is unclear whether this disease is rare or should be considered as an emerging clinical entity.