Cutaneous Locations Research Articles

Differences in the location of bleeding with direct oral anticoagulants vs. vitamin K antagonists: A study in the World Health Organization's pharmacovigilance database.

Clinical trials have found differences in bleeding locations between direct oral anticoagulants (DOAC) and vitamin K antagonists (VKA). The present study was performed to investigate these differences in real life using reports of adverse drug reactions registered in the World Health Organization's pharmacovigilance database, VigiBase®. All bleeding registered between 1 January 2008 and 31 December 2021 in adults were included. The main objective was to compare bleeding locations reported with DOAC with those with VKA. As a secondary objective, we performed the same comparison with Xa vs. thrombin inhibitors. Results were presented as reporting odds ratios (RORs) adjusted on age, gender, origin of reports and co-medications with their 95% confidence interval. During this 14-year period, 142 228 instances of bleeding were registered with oral anticoagulants, including 39 570 with VKA and 102 658 with DOAC. Mean time to event was lower with DOAC (7.6months) than with VKA (29.9months) (P < .001). Significant differences in bleeding locations were found in the reports with less cerebral, urologic and nasal bleeding, more gynaecologic bleeding with DOAC than with VKA, without any significant differences in digestive and cutaneous locations. A higher risk of bleeding reports was found with Xa inhibitors vs. dabigatran whatever the locations (except digestive bleeding). This real-life study shows that the differences in bleeding locations between DOAC and VKA are not limited to the brain or gastrointestinal tracts. Significant differences were also found between Xa and thrombin inhibitors.

Oral Extramedullary Plasmacytoma Treatment Using a Combination of Marginal Excision and Strontium-90 Therapy in Five Dogs.

Extramedullary plasmacytoma (EMP) is a benign round cell tumor that is most commonly found in cutaneous locations in dogs and occurs less frequently in the oral cavity. They are highly radiosensitive, are distinct from systemic multiple myeloma syndrome and wide surgical excision is typically curative. This report describes five cases of non-invasive oral EMP in dogs treated with a combination of marginal excision and strontium-90 plesiotherapy. All five cases had narrow or incomplete margins on histopathologic evaluation but experienced no recurrence after combination therapy. Plesiotherapy radiation may offer a potential adjunct treatment for non-invasive oral EMP by providing a superficial dose of radiation that complements a less invasive surgical removal. The combination of plesiotherapy and marginal excision may offer an alternative to wide surgical excision for non-invasive oral EMPs.

A RARE CASE REPORT OF UNDIFFERENTIATED PLEOMORPHIC SARCOMA WITH CUTANEOUS METASTASES DIAGNOSED ON CYTOLOGY.

Soft Tissue Sarcomas (STS) are rare tumours with dismal prognosis. Undifferentiated Pleomorphic Sarcoma (UPS) was formerly called Malignant Fibrous Histiocytoma (MFH) and reclassied by the World Health Organization (WHO) in 2013. UPS account for 5% of adult soft tissue sarcomas. It usually occurs in elderly with a male predominance and is seen on extremities. Despite of it being highly metastatic, cutaneous metastasis is found to be very rare. Hence we present this case of soft tissue UPS of thigh metastasizing to lung, other soft tissues as well as cutaneous locations diagnosed by Fine Niddle Aspiration Cytology (FNAC).

Rapid embryonic development supports the early onset of gill functions in two coral reef damselfishes.

The gill is one of the most important organs for growth and survival of fishes. Early life stages in coral reef fishes often exhibit extreme physiological and demographic characteristics that are linked to well-established respiratory and ionoregulatory processes. However, gill development and function in coral reef fishes is not well understood. Therefore, we investigated gill morphology, oxygen uptake and ionoregulatory systems throughout embryogenesis in two coral reef damselfishes, Acanthochromis polyacanthus and Amphiprion melanopus (Pomacentridae). In both species, we found key gill structures to develop rapidly early in the embryonic phase. Ionoregulatory cells appear on gill filaments 3-4 days post-fertilization and increase in density, whilst disappearing or shrinking in cutaneous locations. Primary respiratory tissue (lamellae) appears 5-7 days post-fertilization, coinciding with a peak in oxygen uptake rates of the developing embryos. Oxygen uptake was unaffected by phenylhydrazine across all ages (pre-hatching), indicating that haemoglobin is not yet required for oxygen uptake. This suggests that gills have limited contribution to respiratory functions during embryonic development, at least until hatching. Rapid gill development in damselfishes, when compared with that in most previously investigated fishes, may reflect preparations for a high-performance, challenging lifestyle on tropical reefs, but may also make reef fishes more vulnerable to anthropogenic stressors.

Occurrence of Cutaneous Neoplasia in Dogs with Actinic Dermatitis in a Veterinary Medical Teaching Hospital - UFRGS, Brazil

Background: Actinic dermatitis is an environmental skin disease resulting from excessive exposure to ultraviolet light irradiated by the sun. This phototoxic reaction affects dogs and cats, particularly with short hair and lightly pigmented skin, exposed to sun light. Primary lesions are typical from a sunburn and chronic exposure, and may induce to a premalignant lesion known as actinic keratosis, which may develop to neoplasms. The aim of the present study was to describe a retrospective study of actinic dermatitis and the occurrence of cutaneous neoplasia in dogs presented to a Veterinary Medical Teaching Hospital (HCV/UFRGS) in Porto Alegre, Rio Grande do Sul, Brazil in a period of 10 years.Materials, Methods &amp; Results: A retrospective review of medical records from January 2009 to December 2019 was performed to identify dogs with actinic dermatitis. Twenty-eight dogs were diagnosed based on a history of sun exposure and skin lesions including erythema, scaling, comedones, thickened skin, hyperpigmentation, ulceration and/or secondary infections on poorly pigmented skin. In addition, in twelve dogs (42.8%) the disease was also confirmed by histopathology. Cutaneous lesions locations were previously defined as head, limbs, neck and trunk. The head was subdivided in chin, ears, face, lips and nasal plane; the limbs in pelvic and thoracic; and the trunk, in abdomen, dorsal pelvis, perianal and thorax. All 28 dogs diagnosed with actinic dermatitis in the study had been chronically exposed to solar radiation and had light skin and coat. Dogs were between 3 and 20 years old, mean 7.6 years and median 7 years, mostly female dogs (64.2%) and neutered or spayed (64.2%). The most affected breeds were American Pitbull Terrier (35.7%) and Boxers (28.5%). Other breeds were Bull Terrier, Dalmatian, Dogo Argentino and Scottish Terrier. In 15 cases, tumors were confirmed by cytopathology or histopathology, resulting in 9 different skin tumors and two types of cysts (epidermoid and follicular). Among these, the most prevalent malignant neoplasm was squamous cell carcinoma (66.7%), followed by mast cell tumor (40%), hemangiosarcoma (26.6%), and basal cell carcinoma (6.6%). Five benign tumors were identified: hemangioma (13.3%), fibroma (6.6%), lipoma (6.6%), sebaceous adenoma (6.6%) and trichoepithelioma (6.6%). The most prevalent location for actinic lesions was the trunk (92.8%), being more prevalent on the ventral abdomen (82.1%). Actinic lesions were also present on head, neck and limbs. In 13/15 patients (86.6%), actinic lesions and at least one neoplasia location matched.Discussion: Actinic dermatitis tends to occurs in mid-aged to senile dogs because of the disease progressive and chronic behavior and owners delay to detect early clinical signs. In fact, actinic dermatitis was diagnosed at the average age of 7.6 years in the present study. The skin lesions were mostly located on light hair areas and were not observed on pigmented skin. The trunk (mainly the abdomen) had higher frequency of skin lesions compared to other anatomic areas, possibly because some dogs like to sunbathe at dorsal or lateral recumbency, some floor types can reflect sunlight, and some ventral abdomen are hairless. Ultraviolet radiation causes important local and systemic immunogenic changes. The impairment of the immune system and antigen recognition can influence cutaneous susceptibility to develop neoplasm. In conclusion, approximately 50% of the dogs with actinic dermatitis were associated with different skin neoplasm. The most prevalent was squamous cell carcinoma, mast cell tumor and hemangiosarcoma. Actinic lesions and neoplasm matched location in almost all patients with both conditions, however it was not possible to define if solar radiation had predisposed the occurrence of all observed neoplasms. Further studies are needed to prove the influence of ultraviolet radiation in the development of different cutaneous neoplasms.

Cutaneous manifestations of mantle cell lymphoma: an extensive literature review

Mantle cell lymphomas account for about 2 to 10% of non-Hodgkin B-cell lymphomas. Despite the cellular maturity of B-cell lymphomas, the disease is aggressive in the majority of cases and its course is unpredictable. The clinical presentation is variable, and multiple nodal and extranodal manifestations have been described. Cutaneous infiltration is an uncommon (2-6%) location of the disease. An extensive review of the literature was performed, and 24 case reports and five case series were found describing cutaneous locations. These data were thoroughly studied in order to present their clinical and laboratory characteristics in this review.

Association of Nodal Metastasis and Mortality With Vermilion vs Cutaneous Lip Location in Cutaneous Squamous Cell Carcinoma of the Lip

Although the lip is considered a high-risk location in cutaneous squamous cell carcinoma (cSCC), it has not been established whether this risk stems from vermilion or cutaneous locations or both. To compare differences in risks of recurrence, metastasis, and death from cSCCs on the vermilion vs cutaneous lip. Retrospective cohort study of 303 patients with 310 primary cSCCs of the lip (138 cutaneous, 172 vermilion) diagnosed between 2000 and 2015 at 2 academic tertiary care centers in Boston, Massachusetts. Development of local recurrence, nodal metastasis, distant metastasis, disease-specific death, and all-cause death. Of the 303 study participants with 310 SCCs of the lip, 153 (50.5%) were men, and 150 (49.5%) were women; median age at diagnosis, 68 years (range, 27-93 years). Outcomes were as follows for vermilion vs cutaneous locations: local recurrence, 6.4% (11 of 172) vs 2.9% (4 of 138); nodal metastasis, 7.6% (13 of 172) vs 1.5% (2 of 138); distant metastasis, 0.6% (1 of 172) vs 0.7% (1 of 138); disease-specific death, 3.5% (6 of 172) vs 2.9% (4 of 138); and all-cause death, 26.7% (46 of 172) vs 29.0% (40 of 138). The difference was statistically significant for nodal metastasis (P = .01). In multivariable analysis, nodal metastasis was associated with vermilion lip location (subhazard ratio, 5.0; 95% CI, 1.1-23.8) and invasion beyond fat (fascia or beyond for vermilion lip) (subhazard ratio, 4.4; 95% CI, 1.3-14.9). The risk of nodal metastasis is 5-fold greater for cSCCs on the vermilion lip compared with those on the cutaneous lip. Squamous cell carcinomas of the cutaneous lip have a nodal metastasis risk similar to cSCCs in general (1.5%). Thus, vermilion involvement appears responsible for the increased risk associated with cSCC of lip. Vermilion involvement may merit radiologic nodal staging and inclusion in future tumor staging, since it was independently associated with higher-risk cSCC of the lip region.

Does the application site of spinal manipulative therapy alter spinal tissues loading?

Background contextPrevious studies found that the intervertebral disc (IVD) experiences the greatest loads during spinal manipulation therapy (SMT). PurposeBased on that, this study aimed to determine if loads experienced by spinal tissues are significantly altered when the application site of SMT is changed. Study DesignA biomechanical robotic serial dissection study. SampleThirteen porcine cadaveric motion segments. Outcome MeasuresForces experienced by lumbar spinal tissues. MethodsA servo-controlled linear actuator provided standardized 300 N SMT simulations to six different cutaneous locations of the porcine lumbar spine: L2–L3 and L3–L4 facet joints (FJ), L3 and L4 transverse processes (TVP), and the space between the FJs and the TVPs (BTW). Vertebral kinematics were tracked optically using indwelling bone pins; the motion segment was removed and mounted in a parallel robot equipped with a six-axis load cell. Movements of each SMT application at each site were replayed by the robot with the intact specimen and following the sequential removal of spinal ligaments, FJs and IVD. Forces induced by SMT were recorded, and specific axes were analyzed using linear mixed models. ResultsAnalyses yielded a significant difference (p<.05) in spinal structures loads as a function of the application site. Spinal manipulative therapy application at the L3 vertebra caused vertebral movements and forces between L3 and L4 spinal segment in the opposite direction to when SMT was applied at L4 vertebra. Additionally, SMT applications over the soft tissue between adjacent vertebrae significantly decreased spinal structure loads. ConclusionApplying SMT with a constant force at different spinal levels creates different relative kinetics of the spinal segments and load spinal tissues in significantly different magnitudes.

Beyond the Bottom of the Foot: Topographic Organization of the Foot Dorsum in Walking.

Sensory feedback from the foot dorsum during walking has only been studied globally by whole nerve stimulation. Stimulating the main nerve innervating the dorsal surface produces a functional stumble corrective response that is phase-dependently modulated. We speculated that effects evoked by activation of discrete skin regions on the foot dorsum would be topographically organized, as with the foot sole. Nonnoxious electrical stimulation was delivered to five discrete locations on the dorsal surface of the foot during treadmill walking. Muscle activity from muscles acting at the ankle, knee, hip, and shoulder were recorded along with ankle, knee, and hip kinematics and kinetic information from forces under the foot. All data were sorted on the basis of stimulus occurrence in 12 step cycle phases, before being averaged together within a phase for subsequent analysis. Results reveal dynamic changes in reflex amplitudes and kinematics that are site specific and phase dependent. Most responses from discrete sites on the foot dorsum were seen in the swing phase suggesting function to conform foot trajectory to maintain stability of the moving limb. In general, responses from lateral stimulation differed from medial stimulation, and effects were largest from stimulation at the distal end of the foot at the metatarsals; that is, in anatomical locations where actual impact with an object in the environment is most likely during swing. Responses to stimulation extend to include muscles at the hip and shoulder. We reveal that afferent feedback from specific cutaneous locations on the foot dorsum influences stance and swing phase corrective responses. This emphasizes the critical importance of feedback from the entire foot surface in locomotor control and has application for rehabilitation after neurological injury and in footwear development.

Induction of α6 and β1 integrins by acupuncture stimulation in rats

Acupuncture therapy is performed by applying the needle insertion at discrete cutaneous locations and used for the treatments of diverse symptoms and disorders. In order to elucidate mechanistic basis on how acupuncture stimulation (AS) produces therapeutic effects, it is primarily important to understand tissue responses locally at the acupuncture site (acupoint). Here, we investigated integrin protein as molecular target responding to and integrating AS. Signals of α6 and β1 integrins were clearly induced at zusanli acupoint 24 h after AS in areas of nuclear clusters around the needle track. Induction levels of integrin were largely reduced by needle insertion at non-acupuncture point or without needle rotation. Phospho-Erk1/2 was initially decreased below the basal level after AS but increased 24 h later. Induction pattern of phospho-Erk1/2 was as similar as that of α6 integrin in its selectivity to needling procedure and tissue distribution. We further found that mRNA expression of P2X3 purinergic receptor was upregulated in the dorsal root ganglion (DRG) after AS, but decreased by the inhibition of Erk1/2 activity at the acupuncture area. Moreover, AS-mediated integrin activation was required for Erk1/2 activation at the acupuncture site and regulation of pain sensitivity in the hind paw. The present results provide a new evidence on acupuncture-specific tissue response in terms of integrin induction, and further suggest that integrin activation may be involved in transmitting mechanosensory signals from the acupoint to afferent nerve fiber.

Influence of Spinal Manipulative Therapy Force Magnitude and Application Site on Spinal Tissue Loading: A Biomechanical Robotic Serial Dissection Study in Porcine Motion Segments

ObjectiveIn order to define the relation between spinal manipulative therapy (SMT) input parameters and the distribution of load within spinal tissues, the aim of this study was to determine the influence of force magnitude and application site when SMT is applied to cadaveric spines. MethodsIn 10 porcine cadavers, a servo-controlled linear actuator motor provided a standardized SMT simulation using 3 different force magnitudes (100N, 300N, and 500N) to 2 different cutaneous locations: L3/L4 facet joint (FJ), and L4 transverse processes (TVP). Vertebral kinematics were tracked optically using indwelling bone pins, the motion segment removed and mounted in a parallel robot equipped with a 6-axis load cell. The kinematics of each SMT application were replicated robotically. Serial dissection of spinal structures was conducted to quantify loading characteristics of discrete spinal tissues. Forces experienced by the L3/L4 segment and spinal structures during SMT replication were recorded and analyzed. ResultsSpinal manipulative therapy force magnitude and application site parameters influenced spinal tissues loading. A significant main effect (P < .05) of force magnitude was observed on the loads experienced by the intact specimen and supra- and interspinous ligaments. The main effect of application site was also significant (P < .05), influencing the loading of the intact specimen and facet joints, capsules, and ligamentum flavum (P < .05). ConclusionSpinal manipulative therapy input parameters of force magnitude and application site significantly influence the distribution of forces within spinal tissues. By controlling these SMT parameters, clinical outcomes may potentially be manipulated.

Pathology and classification of aggressive mature B-cell lymphomas.

Pathology and classification of aggressive mature B-cell lymphomas.

The distribution of cutaneous metastases correlates with local immunologic milieu

Metastases to the skin are found with increased frequency at certain sites, such as the scalp, but the biological factors that influence this distribution are not understood. We aimed to compare the proportional frequency of metastases at various cutaneous locations with the immunologic microenvironments at those sites. We retrospectively identified all biopsy specimens of cutaneous metastases diagnosed at our institution from 1991 to 2014 (n = 1984) and mapped their anatomic distribution while controlling for regional surface area. Using a separate, mapped cohort of normal-appearing skin samples (n = 140), we measured the density of regulatory T cells, CD4(+) effector T cells, and CD8(+) T cells by flow cytometry. Per unit surface area, cutaneous metastases arise most commonly on the head and neck, followed by the trunk, upper extremities, and lower extremities, respectively. Sites with more frequent metastases tend to contain a greater density of regulatory T cells and a lower proportion of CD8(+) T cells (P < .05). Immunologic factors were only assessed in control tissue and were not measured from patients with metastatic disease in this correlative single-center study. The distribution of cutaneous metastases follows the distribution of regulatory and effector T cells in skin. Further studies are required to prove a mechanistic association between local immunologic factors and the development of cutaneous metastases.

Naturally acquired bovine besnoitiosis: Differential distribution of parasites in the skin of chronically infected cattle

Bovine besnoitiosis is caused by Besnoitia besnoiti, an apicomplexan parasite closely related to Toxoplasma gondii and Neospora caninum. In the acute stage of besnoitiosis, cattle suffer from pyrexia, swollen lymph nodes, anorexia and subcutaneous edema. In the chronic stage, tissue cysts are formed in a variety of tissues including the skin. Knowledge about the distribution of tissue cysts of different parts of the skin of infected animals is scarce. Four chronically infected cattle were euthanized and skin samples were taken from a total of 77 standardized cutaneous locations per animal. Portions of the dermis were taken, from which DNA was extracted and examined by real-time PCR. Cycle of transition (Ct) values reflecting the amount of parasite DNA in the samples were determined. For statistical analysis, samples were attributed to 11 larger skin regions (‘OuterHindlegDistal’, ‘Rump, ForelegMiddle’, ‘NoseFrontEars’, ‘CheekEye’, ‘SideLowerPart’, ‘ForelegDistal’, ‘SideUpperPart’, ‘LegsInner’, ‘VentralHeadNeck’, ‘DorsalNeckWithersBackTail’). While all samples revealed a positive result in three female cattle, only 63.6% (49/77) of the samples of a bull showed positive results. For statistical analysis, a Ct value of 45 was assumed for samples with a negative result. The dams showed median Ct values of 16.1, 17.5 and 19.4, while in skin samples of the bull a median Ct value of 37.6 was observed. To determine the differences in DNA concentrations between different locations of the skin of the animals, a relative Ct (relCt) was determined by subtracting for each animal indv the MedianCtindv from each sample Ct. Analyses of the relCt values showed that the highest relative parasite DNA concentrations were observed in the categories ‘OuterHindlegDistal’, ‘Rump’, ‘ForelegMiddle’ and ‘NoseFrontEars’. The relCt values in these categories differed statistically significantly from those determined for the categories ‘VentralHeadNeck’ and ‘DorsalNeckWithersBackTail’. The analysis showed clear differences in the distribution and the detectability of parasite DNA in the skin of cattle infected with B. besnoiti. In all four animals, samples from the ‘Rump’ region (Regio fermoris) showed high parasite DNA concentrations. Because this region is also easily accessible for veterinarians, this skin location appears to be optimal for taking skin biopsies for detection or isolation of B. besnoiti.

AN UNUSUAL BUMP ON THE HEAD: INTRAEXTRACRANIAL MENINGIOMA PRESENTING INCIDENTALLY

An 82–year–old gentleman presented to hospital following a fall. The patient had no recollection of the fall, and was found conscious sometime later on the floor by the neighbours. At...

Corticothérapie préalable au diagnostic de leucémie aiguë lymphoblastique (LAL) de l’enfant : effet délétère pour la prise en charge diagnostique et thérapeutique

The aim of this study was to show that steroid therapy taken before the diagnosis of acute lymphoblastic leukemia (ALL) can alter the management of the disease. We conducted a multicenter retrospective study on 11 children treated between 2005 and 2011, who received oral steroids ranging from 0.6 to 3.3mg/kg/day prednisolone equivalent for a duration of 2 to 15 days during the 2 months prior to diagnosis of ALL. Four children had febrile pancytopenia. Among them, 2 had severe infections and a noncontributive bone marrow aspiration. One of them presented a severe tumoral lysis syndrome and was hospitalized twice in the intensive care unit. Two teenagers had central nervous system involvement at diagnosis of T-ALL, 1 having associated cutaneous locations, the second one showing pulmonary and central nervous system (CNS) leukostasis with renal failure and disseminated intravascular coagulation. One child died of septic shock during the induction phase of steroid-resistant T-ALL. Four children had no complications during the induction phase. Steroid resistance occurred in 5 cases and steroid sensitivity could not be evaluated in 3 cases. Three allogeneic bone marrow transplants were performed: the first one because of early CNS relapse, the 2 others because of initial treatment resistance. Steroids can induce a delay in the management of ALL and seem to favor initial complications, and possibly increase diffuse locations as well as steroid resistance. Their prescription needs to be carefully managed, especially for uncharacteristic infectious symptoms. Then a complete blood count should be done.

Small Demodex populations colonize most parts of the skin of healthy dogs

It is unproven that all dogs harbour Demodex mites in their skin. In fact, several microscopic studies have failed to demonstrate mites in healthy dogs. Demodex canis is a normal inhabitant of the skin of most, if not all, dogs. This hypothesis was tested using a sensitive real-time PCR to detect Demodex DNA in the skin of dogs. One hundred dogs living in a humane society shelter, 20 privately owned and healthy dogs and eight dogs receiving immunosuppressive or antineoplastic therapy. Hair samples (250-300 hairs with their hair bulbs) were taken from five or 20 skin locations. A real-time PCR that amplifies a 166 bp sequence of the D. canis chitin synthase gene was used. The percentage of positive dogs increased with the number of sampling points. When a large canine population was sampled at five cutaneous locations, 18% of dogs were positive for Demodex DNA. When 20 skin locations were sampled, all dogs tested positive for mite DNA. Our study indicates that Demodex colonization of the skin is present in all dogs, independent of age, sex, breed or coat. Nevertheless, the population of mites in a healthy dog appears to be small. Demodex DNA was amplified from all 20 cutaneous points investigated, without statistically significant differences. Using a real-time PCR technique, Demodex mites, albeit in very low numbers, were found to be normal inhabitants of haired areas of the skin of healthy dogs.

Extraocular lymphoma in the horse

To describe the clinical findings and prognosis for extraocular lymphoma in the horse. Retrospective medical records study of horses diagnosed with third eyelid, corneoscleral, conjunctival, and/or eyelid lymphoma from multiple academic and private veterinary institutions. Data collected from the medical records included signalment, clinical descriptions of the extraocular lesions, treatment, and treatment outcomes. Nonparametric statistical analysis was performed with Fischer's exact tests. Extraocular lymphoma involving the eyelid, third eyelid, cornea, sclera, and/or conjunctiva was diagnosed in 26 horses. Differences in signalment, unilateral vs. bilateral extraocular involvement, and single vs. multiple extraocular lesion locations held no significance in terms of outcome. Horses with lesions localized to the eyelid or other nonextraocular cutaneous locations had a significantly higher chance of negative outcome when compared to the horses with no eyelid or cutaneous involvement (P = 0.019). Lesions to the third eyelid, corneosclera, and conjunctiva were either nodular or diffuse in nature. Nodular lesions when compared to diffuse lesions were associated with a higher chance of a positive outcome (P = 0.007). Surgical resection of the extraocular lesions as part of the treatment produced a statistically higher chance of a positive outcome when compared to horses where resection was not performed (P = 0.03). The prognosis for clinical remission in horses with extraocular lymphoma is generally fair to good, as long as the affected tissues are completely excised, and there is no eyelid or cutaneous involvement. Horses diagnosed with the nodular form of extraocular lymphoma seem to have the best prognosis with complete excision.

Ecallantide for treatment of acute hereditary angioedema attacks: Analysis of efficacy by patient characteristics

Hereditary angioedema (HAE) is characterized by episodic attacks of edema. HAE is caused by low levels of the protein C1 esterase inhibitor, which inhibits plasma kallikrein, the enzyme responsible for converting high-molecular-weight kininogen to bradykinin. Unregulated production of bradykinin leads to the characteristic clinical symptoms of swelling and pain. Ecallantide is a novel plasma kallikrein inhibitor effective for treatment of acute HAE attacks. This study was designed to analyze the efficacy of ecallantide for treating HAE attacks by attack location, attack severity, patient gender, and body mass index (BMI). An analysis of integrated data from two double-blind, placebo-controlled trials of ecallantide for treatment of acute HAE attacks was undertaken. For the purpose of analysis, symptoms were classified by anatomic location and, for each location, by the patient-assessed severity of the attack. Efficacy versus placebo was examined using two validated patient-reported outcomes: treatment outcome score and mean symptom complex severity score. One hundred forty-three attacks were analyzed (73 ecallantide and 70 placebo). Ecallantide was equally effective in both male and female subjects. Ecallantide had decreased efficacy for patients with BMI > 30 kg/m(2). Ecallantide showed efficacy for treatment of severe and moderate attacks, and was effective for abdominal, internal head and neck, external head and neck, and cutaneous locations. In summary, ecallantide is effective for treatment of acute HAE attacks of different symptom locations and severity; outcomes were similar for men and women. However, the standard dose was less effective for obese patients.

Urban Transmission of Human African Trypanosomiasis, Gabon

To the Editor: We describe a confirmed case of human African trypanosomiasis (HAT) in an expatriate returning to France from Gabon after a probable tsetse fly bite in the urban setting of Libreville. This case indicates a possible urban transmission of HAT in Gabon and stresses the need for entomologic studies in Libreville. HAT is endemic to sub-Saharan Africa. Trypanosoma brucei rhodesiense (eastern Africa) and T.b. gambiense (western Africa) parasites are transmitted to humans by tsetse flies of the Glossina morsitans group (T.b. rhodesiense) and of the G. palpalis group (T.b. gambiense), which are found only in Africa. T.b. gambiense represents >90% of all reported cases of HAT worldwide. HAT has always been a travel-associated disease. It is a rare cause of fever, cutaneous lesions, and neurologic signs in travelers returning from disease-endemic areas and involves T.b. rhodesiense in 70% of the cases, resulting mostly from an exposure during safari in game parks (1,2). A 58-year-old previously healthy Portuguese man who worked in Gabon for 13 years for a French company was admitted to the tropical and infectious diseases ward because of a 2-month history of intermittent fever, fatigue, and a 10-kg weight loss. The patient recalled a painful unidentified insect bite on his right thigh 2 months before in his garden in Libreville (Lalala quarter). A 8-cm, indurated, erythematous, and painful plaque (chancre) progressively developed (Figure) in the following weeks after the assumed insect bite. When admitted to the hospital, the patient had a temperature of 39°C, anorexia, insomnia, pruritus of the left arm, and paresthesia of the hands and feet. Two additional large annular erythematous macules, centrally pale (trypanids), were found on his back (Figure). A subclavicular 0.5-cm lymph node was observed. There was no hepatosplenomegaly. Figure Thigh chancre (1) and back trypanids (2 and 3) in a patient with human African trypanosomiasis infection, Gabon. His laboratory results showed moderate anemia (hemoglobin 11.8 g/dL) and thrombopenia (134,000 platelets/mm3) and elevated levels of C-reactive protein (30.6 mg/L) and gammaglobulins (23.9 g/L). A thick-blood smear showed no malaria parasites but a few trypomastigotes of Trypanosoma spp. PCR of blood identified T.b. gambiense. A cerebrospinal fluid sample showed moderate elevation of total proteins (0.43 g/L) and albumin (291 mg/L), 11 leukocytes, and no IgM elevation. Direct examination and PCR showed no trypanosome in the cerebrospinal fluid. Specific antibodies were found in the blood by indirect immunofluorescence (titer 200). Biopsies of 2 skin lesions (thigh, back) showed a lymphoplasmocytic vasculitis consistent with cutaneous locations of HAT; no parasite was observed in situ. The patient was treated successfully with a 7-day course of pentamidine. The case was reported to World Health Organization Control of Neglected Tropical Diseases Department. A total of 328 HAT cases were reported to the World Health Organization in Gabon during 2000–2009; most infections were acquired in the mangrove swamp Atlantic coast focus in Noya (Estuaire Province) and some in the focus of Bendje (Ogooue-Maritime Province) (3). Four of 6 cases of T.b. gambiense imported to Europe during 2005–2009 were in expatriates with a travel history to Gabon (1). In the 4 case-patients infected in Gabon, an exposure in rural forest areas was assessed (4–6; D. Malvy, pers. comm.). In the fifth case reported here, the tsetse bite likely occurred in the urban setting of Libreville. The patient did not report occupational exposure to tsetse bites outside Libreville during the previous year. He occasionally went in Pointe Denis during weekends but did not remember having been bitten by a tsetse fly. Although the patient did not identify the insect in his garden, the chronology of his clinical history and the presence of a typical chancre at the place of the insect bite that occurred before symptoms provide strong arguments in favor of this hypothesis. The bite occurred during the morning hours, in the patient’s home garden in the Lalala area of Libreville (0.357568N, 9.475365E) near the Ogombie River. This area is located 125 km and 75 km from the Bendje and Noya HAT foci, respectively. Two studies provided evidence for urban transmission of HAT in Kinshasa (Democratic Republic of Congo) and in Bonon (Cote d’Ivoire) (7,8). Concurrently, some tsetse species, such as G. palpalis, adapt to high human densities and are found in the largest urban centers of western Africa (9). Entomologic studies in Libreville should prompt further investigation into a possible urban transmission of HAT in Gabon, as we suspect in the case reported.