Características clínicas de los pacientes con fiebre manchada de las Montañas Rocosas, infección por dengue y chikungunya / Clinical features of patients with Rocky Mountain spotted fever, dengue and chikungunya infection

Resumen Introducción: La distinción clínica entre infecciones arbovirales y las provocadas por rickettsias es crucial para iniciar el tratamiento médico apropiado. Objetivo: Comparar las diferencias entre fiebre manchada de las Montañas Rocosas (FMMR) y otras enfermedades transmitidas por vector (dengue y chikungunya) con presentación clínica similar e identificar los datos que pudieran ayudar al diagnóstico rápido de esas enfermedades. Métodos: Se evaluaron datos sociodemográficos, clínicos y de laboratorio de 399 pacientes de cinco hospitales y clínicas en Sonora, México, entre 2004 y 2016, con el diagnóstico confirmado por laboratorio de FMMR, dengue o chikungunya. Resultados: El grupo con FMMR presentó la mayor letalidad (49/63 muertes, 77.8 %), seguido por el de chikungunya (3/161, 1.9 %) y el de dengue (3/161, 1.9 %). Las diferencias clínicas consistieron en la presencia de exantema, edema y prurito; además, se documentaron diferencias en múltiples biomarcadores como plaquetas, hemoglobina, bilirrubina indirecta y niveles de sodio sérico. Conclusión: El exantema en palmas y plantas, edema y ausencia de prurito, aunados a niveles altos de bilirrubina directa y trombocitopenia severa pudieran ser indicadores útiles para diferenciar a pacientes con FMMR en etapas avanzadas de aquellos con dengue y chikungunya.

Abstract Introduction: Clinical distinction between arbovirus infections and those caused by rickettsia is crucial to initiate appropriate medical treatment. Objective: To compare the differences between Rocky Mountain spotted fever (RMSF) and other vector-borne diseases (dengue and chikungunya) with similar clinical presentation, and to identify data that could aid rapid diagnosis of these diseases. Methods: Sociodemographic, clinical and laboratory data of 399 patients from five hospitals and clinics of Sonora, Mexico, with laboratory-confirmed diagnosis of RMSF, dengue, or chikungunya between 2004 and 2016 were evaluated. Results: The RMSF group had the highest lethality (49/63 deaths, 77.8 %), followed by the chikungunya group (3/161, 1.9 %) and the dengue group (3/161, 1.9 %). Clinical differences included the presence of rash, edema, and pruritus; in addition, differences in multiple biomarkers such as platelets, hemoglobin, indirect bilirubin, and serum sodium levels were documented. Conclusion: Rash on the palms and soles, edema and absence of pruritus, together with high levels of direct bilirubin and severe thrombocytopenia could be useful indicators to differentiate patients at RMSF advanced stages from those with dengue and chikungunya.

Long term neurologic sequelae in a Mexican rocky mountain spotted fever case

ABSTRACT During the second half of the twentieth century, neurologic sequelae associated with central nervous system impairment caused by Rickettsia rickettsii were studied widely and exclusively in the United States. We present the case of a Mexican pediatric patient with neurologic sequelae 10 years after an acute infection by R. rickettsii.

Caso fulminante de rickettsiosis (Rickettsia rickettsii) en una lactante del sureste de México / Fatal case of rickettsiosis in a toddler from southeastern Mexico

La fiebre manchada de las Montañas Rocosas es una enfermedad ocasionada por Rickettsia rickettsii, una bacteria transmitida por garrapatas infectadas, y que se caracteriza por fiebre, exantema, artralgias y mialgias, aunque, ocasionalmente, su presentación es inespecífica. Debido a que su evolución asemeja otras enfermedades exantemáticas, como dengue o chikungunya, su diagnóstico no es de primera intención, a pesar de que países como México tienen las características ecológicas y socioeconómicas propicias para su transmisión, con índices de mortalidad hasta de 30% en pacientes pediátricos. Esta elevada mortalidad se asocia a diagnósticos y terapia retrasados debido al desconocimiento médico acerca de la enfermedad, lo que propicia la aparición de formas atípicas y fulminantes de fiebre manchada de las Montañas Rocosas. El objetivo del presente trabajo es describir un caso clínico fulminante de fiebre manchada de las Montañas Rocosas para que sea considerada en el diagnóstico diferencial, lo cual impactaría directamente en los índices de mortalidad.

Rocky Mountain spotted fever is a disease caused by Rickettsia rickettsii, a bacteria transmitted by infected ticks. It is characterized by fever, exanthema, arthralgias and myalgias; but sometimes its clinical presentation is non specific. Due to its similarities with other exanthematic diseases like dengue or chikungunya, Rocky Mountain spotted fever is not a first line diagnosis, even though countries like Mexico show the ecologic and socioeconomic characteristics that favor its transmission, with a 30% mortality rate among pediatric patients. This mortality rate has been associated to a delayed diagnosis and therapy, due to a poor knowledge among physicians regarding this disease; this favors the occurrence of atypical and fulminant cases. The objective of this work is to describe a fulminant case of Rocky Mountain spotted fever, expecting that this disease could be later considered among the differential diagnosis which could directly impact its mortality rate.

Fiebre manchada grave por Rickettsia rickettsii en turista en el Noroeste Argentino / Severe spotted fever by Rickettsia rickettsii, in tourist in the Argentine Northwest

Al quinto día de retirarse del Parque Nacional El Rey, provincia de Salta, Argentina, donde realizó turismo rural, una mujer italiana de 47 años desarrolló un cuadro febril agudo seguido de un exantema petequial y purpúrico que progresó rápidamente a falla multiorgánica y falleció al sexto día de internación. Existieron referencias a mordeduras por garrapatas y se constató una lesión cutánea similar a la denominada tache noire. La autopsia mostró una vasculitis generalizada, ascitis, edema de pulmón, necrosis tubular aguda y necrosis portal centrolobulillar. Se procesó tejido esplénico y hepático con técnica de PCR para Rickettsia spp, basada en la detección del gen gltA. El resultado fue positivo. Los amplicones obtenidos fueron secuenciados y los resultados se compararon con las secuencias preestablecidas en el programa BLAST, coincidiendo en un 99% con R. rickettsii. La baja sensibilidad del sistema de salud en reconocer la enfermedad y la insuficiente información producida desde los medios relacionados con el turismo, son factores que inciden en el retardo de implementar un tratamiento eficaz y las normas de prevención adecuadas.

On the fifth day after leaving the Parque Nacional El Rey, province of Salta, Argentina, where she made rural tourism, a woman of Italian origin, aged 47, developed an acute fever followed by a petechial and purpuric rash that progressed rapidly to multiorgan failure. She died on the sixth day after hospitalization. There were references to tick bites and a skin lesion similar to tache noire was found. The autopsy showed generalized vasculitis, ascites, pulmonary edema, acute tubular necrosis and portal centrilobular necrosis. Spleen and liver tissue were processed for PCR Rickettsia spp, based on the detection of the gltA gene. The result was positive. The amplicons obtained were sequenced and the results were compared with the preset sequences on the BLAST program, 99% coinciding with R. rickettsii. The low sensitivity of the health system to recognize this disease and the insufficient information generated from tourism-related media are factors that affect the delay to implement effective treatment and appropriate prevention standards.

Fiebre maculosa de las Montañas Rocosas en niños y adolescentes mexicanos: cuadro clínico y factores de mortalidad / Rocky Mountain spotted fever in Mexican children: Clinical and mortality factors

Resumen: Objetivo: Caracterizar las manifestaciones clínicas y predictores de mortalidad en niños hospitalizados por fiebre maculosa de las Montañas Rocosas (FMMR). Material y métodos: Estudio transversal en 210 sujetos hospitalizados por FMMR en un hospital pediátrico de Sonora, entre el 1 de enero de 2004 y el 30 de junio de 2015. El análisis se sustentó en estadística descriptiva y regresión logística multivariada. Resultados: Se apreció un incremento en la incidencia y mortalidad en los casos hospitalizados por FMMR, con una letalidad de 30%.Tres variables se asociaron con el riesgo de muerte: retraso ≥ 5 días en el inicio del uso de doxiciclina (RMa=2.95, IC95% 1.10-7.95), falla renal aguda (RMa=8.79, IC95% 3.46-22.33) y sepsis severa (RMa=3.71, IC95% 1.449.58). Conclusión: La FMMR provoca resultados fatales en niños, que puede evitarse con la administración oportuna de doxiciclina. La falla renal aguda y la sepsis severa son dos predictores de muerte en niños con FMMR.

Abstract: Objective: Characterize clinical manifestations and predictors of mortality in children hospitalized for spotted fever. Materials and methods: Cross-sectional study in 210 subjects with a diagnosis of Rocky Mountain spotted fever (RMSF) in a pediatric hospital in Sonora, from January 1st, 2004 to June 30th, 2015. Data were analyzed using descriptive statistics and multivariate logistic regression. Results: An upward trend was observed in RMSF morbidity and mortality. Fatality rate was 30%.Three predictors were associated with risk of death: delay ≥ 5 days at the start of doxycycline (ORa= 2.95, 95% CI 1.10-7.95), acute renal failure ((ORa= 8.79, 95% CI 3.46-22.33) and severe sepsis (ORa= 3.71, 95% CI 1.44-9.58). Conclusions: RMSF causes high mortality in children, which can be avoided with timely initiation of doxycycline. Acute renal failure and severe sepsis are two independent predictors of death in children with RMSF.

Life-threatening ANCA-positive vasculitis associated with rickettsial infection.

We present a 47-year-old Caucasian fire fighter who developed multisystem organ failure in the setting of a positive antineutrophil cytoplasmic autoantibody (myeloperoxidase) as well as confirmed Rocky Mountain spotted fever by skin biopsy PCR. This case provided a diagnostic challenge, a rare association of a Rickettsia infection and autoimmune vasculitis as well as a unique management approach.

Orchitis in two dogs with Rocky Mountain spotted fever.

Two dogs with testicular swelling were sonographically diagnosed with orchitis and were subsequently diagnosed with Rocky Mountain spotted fever (RMSF). Use of both gray scale and color Doppler sonography allowed for differentiation of orchitis from neoplasia and torsion. While only experimentally induced RMSF is reported to cause orchitis in dogs, it should be considered in any dog with vascular insult to the testes, especially when other signs of systemic illness are involved.

Persistence of rickettsiae in the partially viable gangrenous margins of amputated extremities 5 to 7 weeks after onset of Rocky Mountain spotted fever.

A case of Rocky Mountain spotted fever complicated by gangrene of the extremities required amputation and showed persistent rickettsial infection in the margins of the gangrene at 5 and 7 weeks after onset of illness. Rickettsial organisms were demonstrated by immunoperoxidase staining in the viable endothelial cells in the ischemic margins of the gangrenous tissue. We conclude that the cellular, humoral, and pharmacologic components that lead to eradication of the rickettsiae were not delivered to the ischemic margins at effective antirickettsial concentrations.

Acute glomerulonephritis in a patient with Rocky Mountain spotted fever.

It is generally assumed that acute tubular necrosis is the etiology of renal failure that can occur during the course of Rocky Mountain spotted fever (RMSF). However, histologic examination of kidneys has been mainly limited to autopsy cases of fulminant infections. Acute glomerulonephritis due to glomerular immune complex deposition has not been reported in RMSF. We describe a case of acute oliguric renal failure that developed more than 2 weeks following the onset of RMSF. Renal biopsy showed acute glomerulonephritis with inflammatory cell infiltration and subendothelial immune deposits. Thus, acute glomerulonephritis should be in the differential diagnosis of acute renal failure that occurs in RMSF.

The ocular manifestations of Rocky Mountain spotted fever.

To our knowledge, this is the first report of an iris nodule in a case of Rocky Mountain spotted fever (RMSF). The iris nodule may be similar to the "typhus nodule" of the central nervous system reported at autopsy in patients with typhus rickettsial disease. Previous case reports of RMSF have emphasized either anterior uveitis or retinal vasculitis. In the case reported here, both occurred in our patient as a result of RMSF. Also, we review the ophthalmic literature on rickettsial disease.

Pulmonary pathology of Rocky Mountain spotted fever (RMSF) in children.

Despite infrequent respiratory symptoms, histopathologic changes were identified in the lungs of 15 of 16 children dying of Rocky Mountain spotted fever (RMSF). Gross examination demonstrated increased lung weight, edema, congestion, focal hemorrhage, and bronchopneumonia in a few cases. Paraffin sections were stained with hematoxylin and eosin and phosphotungstic acid-hematoxylin, and available blocks were examined by direct immunofluoresence for Rickettsia rickettsii. Cases and controls matched for age and sex were randomized and examined blindly for pathologic changes. In addition, morphometric measurements of mean alveolar septal thickness were made in each case. The histopathologic findings include (1) diffuse interstitial mononuclear (lymphocyte and macrophage) inflammatory infiltrate in 15/16 cases of RMSF (5/10 controls), (2) pulmonary edema and intraalveolar hemorrhage in 11/16 cases of RMSF (2/10 controls), and (3) vasculitis of small pulmonary venules and arterioles in 5/16 RMSF cases (0/10 controls). Rickettsia rickettsii were identified in 4/8 RMSF cases by direct fluorescent antibody technique. Although pulmonary disease is not always clinically apparent in children with RMSF, involvement of the pulmonary microcirculation is a frequent event in fatal cases and may contribute to the development of non-cardiogenic pulmonary edema.

Activation of the kallikrein-kinin system in Rocky Mountain spotted fever.

Activation of the kallikrein-kinin system, as indicated by increased plasma kallikrein and depleted plasma kininogen, prekallikrein, and kallikrein inhibitor, was observed in five patients with Rocky Mountain spotted fever. Four of the patients had petechial rashes characteristic of vasculitis. Three patients had alterations in coagulation consistent with disseminated intravascular coagulation, although no hemorrhagic syndrome was found. Our data, along with the known physiologic actions of kinins, suggest a possible role for the kallikrein-kinin system in the pathophysiology of vasculitis, disseminated intravascular coagulation, circulatory shock, and other complications of infection with Rickettsia rickettsii.

Rocky Mountain spotted fever and jaundice. Two consecutive cases acquired in Florida and a review of the literature on this complication.

Rocky mountain spotted fever is increasing in Florida, a state that has had few cases in the past. The typical clinical illness has been well described, but jaundice has been rarely reported. In two patients with illnesses resembling leptospirosis, jaundice appeared on the sixth and ninth day of illness, and peak bilirubin levels were between 7 and 9 mg/100 ml. Liver biopsy specimen from one patient showed a nonspecific hepatitis. Hemolysis and renal dysfunction may have contributed to the production of jaundice in these patients. Fourteen instances of jaundice were reported in 43 autopsied cases as of 1941, but since that time only rare mention of jaundice has been made.