Lepromatous leprosy: a review and case report

Leprosy is a contagious and chronic systemic granulomatous disease caused by Mycobacterium leprae (Hansen"s bacillus). It is transmitted from person to person and has a long incubation period (between two and six years). The disease presents polar clinical forms (the"multibacillary" lepromatous leprosy and the"paucibacillary" tuberculoid leprosy), as well as other intermediate forms with hybrid characteristics. Oral manifestations usually appear in lepromatous leprosy and occur in 20-60% of cases. They may take the form of multiple nodules (lepromas) that progress to necrosis and ulceration. The ulcers are slow to heal, and produce atrophic scarring or even tissue destruction. The lesions are usually located on the hard and soft palate, in the uvula, on the underside of the tongue, and on the lips and gums. There may also be destruction of the anterior maxilla and loss of teeth. The diagnosis, based on clinical suspicion, is confirmed through bacteriological and histopathological analyses, as well as by means of the lepromin test (intradermal reaction that is usually negative in lepromatous leprosy form and positive in the tuberculoid form). The differential diagnosis includes systemic lupus erythematosus, sarcoidosis, cutaneous leishmaniasis and other skin diseases, tertiary syphilis, lymphomas, systemic mycosis, traumatic lesions and malignant neoplasias, among other disorders. Treatment is difficult as it must be continued for long periods, requires several drugs with adverse effects and proves very expensive, particularly for less developed countries. The most commonly used drugs are dapsone, rifampicin and clofazimine. Quinolones, such as ofloxacin and pefloxacin, as well as some macrolides, such as clarithromycin and minocyclin, are also effective. The present case report describes a patient with lepromatous leprosy acquired within a contagious family setting during childhood and adolescence

The updated Swiss guidelines 2016 for the treatment and follow-up of cutaneous melanoma.

Cutaneous melanoma is the most deadly cutaneous neoplasm. In order to guide treatment decisions and follow-up of melanoma patients, guidelines for the management of melanoma in Switzerland were inaugurated in 2001 and revised in 2006 and 2016. Recent data on surgical and medical treatments from randomised trials necessitated modification of the treatment and follow-up recommendations.

Presence of Leishmania RNA Virus 1 in Leishmania guyanensis Increases the Risk of First-Line Treatment Failure and Symptomatic Relapse.

Treatment failure and symptomatic relapse are major concerns in American tegumentary leishmaniasis (TL). Such complications are seen frequently in Leishmania guyanensis infections, in which patients respond variously to first-line antileishmanials and are more prone to develop chronic cutaneous leishmaniasis. The factors underlying this pathology, however, are unknown. Recently, we reported that a double-stranded RNA virus, Leishmania RNA virus 1 (LRV1), nested within L. guyanensis parasites is able to exacerbate experimental murine leishmaniasis by inducing a hyperinflammatory response. This report investigates the prevalence of LRV1 in human L. guyanensis infection and its effect on treatment efficacy, as well as its correlation to symptomatic relapses after the completion of first-line treatment. In our cohort of 75 patients with a diagnosis of primary localized American TL, the prevalence of LRV1-positive L. guyanensis infection was elevated to 58%. All patients infected with LRV1-negative L. guyanensis were cured after 1 dose (22 of 31 [71%]) or 2 doses (31 of 31 [100%]) of pentamidine. In contrast, 12 of 44 LRV1-positive patients (27%) presented with persistent infection and symptomatic relapse that required extended therapy and the use of second-line drugs. Finally, LRV1 presence was associated with a significant increase in levels of intra-lesional inflammatory markers. In conclusion, LRV1 status in L. guyanensis infection is significantly predictive (P = .0009) of first-line treatment failure and symptomatic relapse and has the potential to guide therapeutic choices in American TL.

Clinically occult metastases in patients with cutaneous melanoma. Detection with sentinel lymph node biopsy and whole body positron emission tomography

Objective: The aim of this study was to investigate the use of sentinel lymph node biopsy (SLNB) and whole body positron emission tomography (PET), with emphasis on surgical treatment and prognosis, in the detection of clinically occult metastases in patients with clinically localized cutaneous melanoma. Patients and methods: The study population consisted of 1255 patients with clinical stage I–II cutaneous melanoma, operated at Turku University Hospital between 1983 and 2007. 334 patients underwent SLNB and they were compared to 921 retrospective patients. A subgroup of 30 symptom-free patients with high risk melanoma underwent prospectively whole body PET 6–24 months postoperatively. Results: Overall, the disease-specific survival rate was 84.4 % at five years. Sex, Breslow thickness, age and nodal status were independent prognostic factors for survival. SLNB revealed occult nodal metastases in 17 % of the patients. There was no significant difference in disease-specific overall survival between SLNB patients and controls, but the nodal disease-free time was significantly longer suggesting better local control after SLNB and subsequent completion lymph node dissection. The followup time was different between the study cohorts and initial surgery was performed during different time periods. SLNB detected micrometastases in seven of 155 patients (4.5 %) with thin T1 primary melanoma and in four of 25 patients (16 %) with head and neck melanoma. In six of 30 asymptomatic patients with high risk melanoma (20 %), whole body PET detected occult distant metastases. Conclusion: Both SLNB and whole body PET were reliable methods to detect clinically occult metastases in patients with cutaneous melanoma. This upstaging altered the treatment in each case.

The regulation and function of collagenase-3 (MMP-13) in cutaneous wound healing and squamous cell carcinoma

Matrix metalloproteinase-13 (MMP-13) is a potent proteolytic enzyme, whose expression has been previously associated with fetal bone development and postnatal bone remodeling and with adult gingival wound healing. MMP-13 is also known to be involved in the growth and invasion of various cancers including squamous cell carcinoma (SCC) of the skin. The aim of this study was to further elucidate the function and regulation of MMP-13 in wound repair and cancer. In this study, it was shown that fetal skin fibroblasts express MMP-13 in response to transforming growth factor-β in a p38 MAP kinase dependent manner. In addition, MMP-13 was found to be expressed in vivo by wound fibroblasts in human fetal skin grafted on SCID mice. Adenovirally delivered expression of MMP-13 enhanced collagen matrix contraction by fibroblasts in vitro in association with altered cytoskeletal structure, enhanced proliferation and survival. These results indicate that MMP-13 is involved in cell-mediated collagen matrix remodeling and suggest a role for MMP-13 in superior matrix remodeling and scarless healing of fetal skin wounds. Using an MMP-13 deficient mouse strain, it was shown that MMP-13 is essential for the normal development of experimental granulation tissue in mice. MMP-13 was implicated in the regulation of myofibroblast function and angiogenesis and the expression of genes involved in cellular proliferation and movement, immune response, angiogenesis and proteolysis. Finally, epidermal mitogen, keratinocyte growth factor (KGF) was shown to suppress the malignant properties of skin SCC cells by downregulating the expression of several target genes with potential cancer promoting properties, including MMP-13, and by reducing SCC cell invasion. These results provide evidence that MMP-13 potently regulates cell viability, myofibroblast function and angiogenesis associated with wound healing and cancer. In addition, fibroblasts expressing MMP-13 show high collagen reorganization capacity. Moreover, the results suggest that KGF mediates the anti-cancer effects on skin SCC

Spatial distribution of canine Visceral Leishmaniasis in Ilha Solteira, São Paulo, Brazil

Visceral Leishmaniasis (VL) is caused by protozoan of genus Leishmania and transmitted by sand flies of genus Lutzomyia, which has been adapted to the peridomicile environment where dogs are their mainly food source, increasing the risk for human cases. In this study, techniques of geoprocessing and spatial statistics were utilized as a contribution to understanding the epidemiological dynamics of VL in the urban area of Ilha Solteira, SP.

Evaluation of outpatient discharge in patients with cutaneous melanoma

OBJECTIVE: to evaluate discharge in a group of patients with cutaneous melanoma according to recently established criteria. METHODS: we conducted an observational, cross-sectional study with 32 patients at the Hospital Universitário Clementino Fraga Filho (HUCFF) / Universidade Federal do Rio de Janeiro (UFRJ), between 1995 and 2013, in the following stages: IA (17 cases, 53.12%), IB (4 cases, 12.5%), IIA (3 cases, 9.37%), IIC (1 case, 3.12%), IIIB (1 case, 3.12%), IIIC (3 cases, 9.37%), melanomas in situ (2 cases, 6.25%), Tx (1 case, 3.12%). RESULTS: the follow-up time varied from one to 20 years (stage IA), five to 15 years (stage IB), six to 17 years (stage IIA), 20 years (stage IIC), 23 years (stage IIIB) and 14 to 18 years (stage IIIC). One melanoma in situ (subungueal) was discharged in the fourth year of follow-up and the other was promptly discharged. The Tx melanoma was followed for 12 years. We observed no relapses or recurrences in the period. CONCLUSION: although a controversial issue, it was possible to endorse the discharge of the patients since our follow-up time had already exceeded the one recommended by the other authors.

Serological diagnosis of visceral leishmaniasis by an enzyme immunoassay using protein A in naturally infected dogs

A rapid indirect enzyme-linked immunosorbent assay (ELISA) was developed for measuring antibodies against Leishmania chagasi using total antigen from lysed promastigotes. Fifty symptomatic mixed breed dogs from a region of high incidence of visceral leishmaniasis in Brazil were examined. The results showed that in the positive animals, diagnosed by cytological examination, the ELISA using protein A assay system (mean optical density ± SD / 2.078 ± 0.631) detected more antibodies than the anti-IgG assay (mean optical density ± SD / 1.008 ± 0.437), while in the negative animals, the results by both systems were similar. These results suggest that the ELISA assay using protein A peroxidase conjugated could be useful to detect early infected animals in endemic areas, and thus help to control the spread of the infection.

Occurrence of anti-Neospora caninum and anti-Toxoplasma gondii antibodies in dogs with visceral leishmaniasis

Uninfected dogs and those naturally infected with Leishmania chagasi exhibiting different clinical forms of disease were evaluated for the presence of anti-Neospora caninum and anti-Toxoplasma gondii antibodies. Blood samples were collected from 110 mongrel dogs. Sera were tested using the indirect fluorescent antibody test (IFAT), and the animals with visceral leishmaniasis (VL) (n=60) were classified clinically. Out of the 110 sera investigated, 5 (4.5%) were positive for N. caninum (IFAT>50) and 36 (32.7%) for T. gondii (IFAT>16). Anti-L. chagasi antibody titers in asymptomatic dogs (n=10) were found to be significantly lower (P<0.05) than those in oligosymptomatic ones (n=22), which were in turn significantly lower (P<0.05) than those in symptomatic ones (n=28). No association between Leishmania and N. caninum infections was observed. Among dogs infected with L. chagasi, a tendency (P=0.053) towards an association between the infection with T. gondii and the appearance of VL symptoms was observed, suggesting that the clinical manifestation of VL in dogs may enhance their susceptibility to T. gondii. The possible influence of the immunosuppressive status of canine leishmaniasis in the different clinical forms of the disease is discussed.

Histomorphological and immunohistochemical characterization of 172 cutaneous round cell tumours in dogs

This paper describes the use of a panel of antibodies (CD117, CD3, CD79a, CD45, cytokeratin, vimentin and E-cadherin) on formalin-fixed, paraffin-embedded sections of canine cutaneous round cell tumours. Neoplastic tumours were diagnosed by histology and histochemical stains and included 107 mast cell tumours, 31 cutaneous histiocytomas, two localized histiocytic sarcomas, 21 cutaneous lymphomas, three plasma cell tumours, one transmissible venereal tumour and seven unclassified round cell tumours. The histologic diagnosis was modified in 39.5% of the total 172 neoplasms. The staining for CD45 and Ecadherin were variable, and therefore, the final diagnoses of cutaneous histiocytoma and localized histiocytic sarcoma were made based on histology in association with negative results for CD3, CD79a, CD117 and cytokeratin. The cellular origin of unclassified round cell tumours was defined in all cases. Cutaneous B-cell lymphoma and plasma cell tumours were CD79a-positive and could be distinguished from each other by the morphological characteristics. Mast cell tumours and T cell lymphoma were CD117 and CD3 positive, respectively. The positive staining for vimentin and the negative staining for CD3, CD79a, CD117 and cytokeratin favoured the diagnosis of transmissible venereal tumours. Thus, the final diagnosis of cutaneous round cell tumours should be based on the interpretation of immunohistochemical results together with the cellular morphology observed by histology. Therefore, more studies to optimize the specific markers in formalin-fixed, paraffinembedded tissues (especially for histiocytes) are required for definitive diagnosis of round cell tumours in dogs.

Outbreak of autochthonous canine visceral leishmaniasis in Santa Catarina, Brazil

The present study reports the first outbreak of autochthonous canine visceral leishmaniasis in Florianópolis, Santa Catarina, southern Brazil. Following the report of two cases of CVL, the Control Center of Zoonotic Diseases conducted a serological survey by ELISA and IFAT assays in seven districts of the Santa Catarina Island. Eleven seropositive dogs of autochthonous transmission were used in the present study. Infection by Leishmania sp. was confirmed by parasitological examination of bone marrow, liver, spleen and lymph nodes, culture in Schneider's medium and PCR. Leishmania sp. isolates were characterized by PCR-RFLP and hybridization with specific probes, allowing for the identification of Leishmania infantum. Autochthonous transmission of this disease in an area with high tourist traffic presents a major public health concern and signifies the emergence of an important zoonosis in southern Brazil. Therefore, the implementation of surveillance and control measures is imperative to prevent the spread of the disease among the canine population as well as transmission to the human population.

Assessment of the electrocardiogram in dogs with visceral leishmaniasis

As myocarditis and arrhythmias have been shown to occur in both human beings and dogs with leishmaniasis, electrocardiograms of 105 dogs serologically positive for this disease were assessed for rhythm disturbances and changes in ECG waves. A few expressive alterations were seen, including sinus arrest, right bundle branch block, and atrial premature beats in 14.3%, 4.8%, and 4.8% of the studied subjects, respectively. Also, the analysis of ECG waves showed changes suggestive of left atrium and ventricle enlargements, and myocardial hypoxia in some animals. Although cardiac compromise has been previously reported in dogs with leishmaniasis, only a small subset of dogs showed any alteration in the electrocardiogram, which cannot support the occurrence of myocarditis in this investigation.

Identification of canine papillomavirus type 1 (CPV1) DNA in dogs with cutaneous papillomatosis

Canine oral papillomavirus (COPV), also known as Canine Papillomavirus type 1 (CPV1), induces papillomas at the mucous membranes of the oral cavity and at the haired skin of dogs. The classification of Papillomavirus (PV) types is based on the L1 capsid protein and nucleotide sequence; so far, 14 CPV types have been described in several countries, but the molecular characterization of CPV in Brazil is lacking. This study investigated the presence of the PV in seven papillomas from four mixed breed dogs from Londrina/PR, Southern Brazil, by partial sequencing of the L1 gene. Seven exophytic cutaneous lesions were surgically removed and processed for histopathological and molecular characterization. Histopathology confirmed the lesions as viral papillomas due to typical histological features. Polymerase Chain Reaction (PCR) assay using the FAP59 and FAP64 primers targeted the L1 gene followed by sequence analysis of the amplicons identified CPV1 in all evaluated papilloma samples. This study represents the first description of CPV1 DNA associated with canine papillomatosis in Brazil.

Photochemistry and photobiology of actinic erythema: defensive and reparative cutaneous mechanisms

Sunlight is part of our everyday life and most people accept it as beneficial to our health. With the advance of our knowledge in cutaneous photochemistry, photobiology and photomedicine over the past four decades, the terrestrial solar radiation has become a concern of dermatologists and is considered to be a major damaging environmental factor for our skin. Most photobiological effects (e.g., sunburn, suntanning, local and systemic immunosuppression, photoaging or dermatoheliosis, skin cancer and precancer, etc.) are attributed to ultraviolet radiation (UVR) and more particularly to UVB radiation (290-320 nm). UVA radiation (320-400 nm) also plays an important role in the induction of erythema by the photosensitized generation of reactive oxygen species (singlet oxygen (1O2), superoxide (O2.-) and hydroxyl radicals (.OH)) that damage DNA and cellular membranes, and promote carcinogenesis and the changes associated with photoaging. Therefore, research efforts have been directed at a better photochemical and photobiological understanding of the so-called sunburn reaction, actinic or solar erythema. To survive the insults of actinic damage, the skin appears to have different intrinsic defensive mechanisms, among which antioxidants (enzymatic and non-enzymatic systems) play a pivotal role. In this paper, we will review the basic aspects of the action of UVR on the skin: a) photochemical reactions resulting from photon absorption by endogenous chromophores; b) the lipid peroxidation phenomenon, and c) intrinsic defensive cutaneous mechanisms (antioxidant systems). The last section will cover the inflammatory response including mediator release after cutaneous UVR exposure and adhesion molecule expression

CD4+ T cells participate in the nephropathy of canine visceral leishmaniasis

Renal involvement in visceral leishmaniasis (VL) is very frequent. The renal lesions of humans and dogs are similar but their pathogenesis has not been clearly elucidated. There is growing evidence that the cellular immune response is involved in the pathogenesis of immunologically mediated glomerulonephritis. Since T cells could participate in the pathogenesis of nephropathy, in the present study we investigated the possible involvement of CD4+ and CD8+ T cells in the nephropathy of canine VL. Six dogs naturally infected with Leishmania (Leishmania) chagasi from the endemic area in the Northeast of Brazil, the town of Teresina in the State of Piauí, were studied. An expressive inflammatory infiltrate of CD4+ T cells both in glomeruli and in interstitium was present in 4 animals and absent in 2. CD8+ T cells were detected only in one animal. CD4+ T cells alone were observed in 3 animals; when CD8+ T cells were present CD4+ T cells were also present. CD4+ T cells were observed in cases of focal segmental glomerulosclerosis, diffuse membranoproliferative glomerulonephritis, diffuse mesangial proliferative glomerulonephritis and crescentic glomerulonephritis. CD8+ T cells were present only in a case of crescentic glomerulonephritis. Leishmania antigen was detected in glomeruli and in interstitial inflammatory infiltrate in 4 animals and immunoglobulins were observed in 4 dogs. In this study we observed that T cells, in addition to immunoglobulins, are present in the renal lesion of canine VL. Further studies are in progress addressing the immunopathogenic mechanisms involving the participation of immunoglobulins and T cells in canine VL nephropathy.