Sea-fan retinal neovascularization associated with rickettsial retinitis: a case report.

BACKGROUND: Rickettsial disease has been commonly associated with retinitis, retinal vasculitis, and optic nerve involvement, but the development of retinal neovascularization has been very rarely reported. We herein describe a case of rickettsial retinitis complicated with the development of sea-fan retinal neovascularization documented with multimodal imaging, including fundus photography, SS-OCT, fluorescein angiography, and SS-OCT angiography. CASE PRESENTATION: A 26-year-old female with a history of fever one week earlier presented with sudden decreased vision in the left eye. Best-corrected visual acuity (BCVA) was 20/2000 and the patient was diagnosed with rickettsial retinitis along the superotemporal retinal vascular arcade associated with serous retinal detachment and retinal hard exudates. The indirect immunofluorescence test was positive for Rickettsia conorii, and the patient was treated with oral doxycycline (200 mg/day) and oral prednisone (0.75 mg/kg/day, with gradual tapering). Four weeks after presentation, the retinal infiltrate and associated serous retinal detachment had resolved, but retinal hard exudates had increased. A large sea-fan preretinal fibrovascular neovascularization became apparent along the superotemporal retinal vascular arcade, but there was no associated retinal ischemia on fluorescein angiography. The patient received an adjunctive single intravitreal injection of 1.25 bevacizumab. Sequential follow-up examinations showed shrinking of sea-fan retinal neovascularization, a complete resolution of retinal hard exudates, and the development of a self-limited vitreous hemorrhage. On last follow-up, 30 months after intravitreal bevacizumab injection, BCVA was 20/25. CONCLUSION: Patients with rickettsial retinitis may develop a sea-fan retinal neovascularization, with subsequent vitreous hemorrhage, putatively through inflammatory mechanisms. Multimodal imaging including OCT, fluorescein angiography, and OCT-angiography, is highly useful for accurate diagnosis and reliable monitoring of the evolution of retinitis, retinal neovascularization, and other retinal changes. The use of a combination therapy with oral doxycycline and corticosteroids and intravitreal anti-VEGF can improve outcomes.

Granulomatous mastitis caused by Rickettsia species.

Granulomatous mastitis is a rare inflammatory disease of varying etiology. Tuberculosis and cystic neutrophilic granulomatous mastitis caused by Corynebacterium are the best-established infectious examples. Despite the increasing incidence of Rickettsia-related diseases worldwide, granulomatous inflammation of breast parenchyma caused by Rickettsia has not yet been reported. We present a unique case of bilateral granulomatous mastitis documented with mammography, magnetic resonance imaging and core-needle biopsy. The rickettsial etiology of the disease was proved with specific immunohistochemistry and confirmed with DNA extraction, PCR and serology. The lesions completely resolved after a full-course tetracycline treatment. This case report widens the knowledge about the possible clinical manifestations of Rickettsia infection and adds a new bacterium to the list of etiological factors causing granulomatous mastitis.

Follow-up of a Rickettsia felis encephalitis: Some new insights into clinical and imaging features.

Rickettsia felis (R. felis) infection is a cause of unspecified encephalitis. However, the incidence has been underestimated due to the intracellular features of the pathogen and insufficient understanding of its clinical picture. This study reported a case of R. felis infection in a 26-year-old female who only manifested with certain neurological symptoms. With a lack of specific systemic inflammatory symptoms, the diagnosis was initially misdiagnosed as a brain glioma. However, a brain tissue biopsy showed prominent perivascular inflammatory infiltrations, which indicated inflammatory disease. Spinal fluid metagenomic next-generation sequencing (mNGS) was taken after ruling out other common infectious and autoimmune diseases. The results suggested R. felis infection, which was also supported by Weil-Felix reaction in the serum. After the diagnosis was corrected as R. felis encephalitis, the patient was successfully treated with doxycycline and had a good prognosis at the 1-year follow-up.

A case with neurological abnormalities caused by Rickettsia raoultii in northwestern China.

BACKGROUND: The number of new rickettsial species are rapidly increasing, and increasing numbers of Rickettsia raoultii (R. raoultii) infection cases have been detected in humans. However, neurological abnormalities caused by R. raoultii are rarely reported, especially in northwestern China. CASE PRESENTATION: A 36-year-old Kazakh shepherd with an attached tick on part temporalis, presented with right eyelid droop, lethargy, fever, headache, fever (38.0-41.0 °C) and erythematous rash. The examination of cerebrospinal fluid (CSF) showed cerebrospinal pressure of 200 mm H2O, leukocyte count of 300.0 × 106/L, adenosine deaminase of 2.15 U/L, and total protein concentration of 0.93 g/L. The diagnosis of R. raoultii infection was confirmed by six genetic markers, and semi-quantified by enzyme-linked immunosorbent assay for rickettsial antigen. The patient gradually recovered after treatment with doxycycline and ceftriaxone. R. raoultii DNA was found both in a tick detached from this patient and in 0.18% (2/1107) of blood samples collected from local shepherds. CONCLUSIONS: This is the first reported case with neurological abnormalities caused by R. raoultii in northwestern China. It is vital to detect rickettsial agents both in blood and CSF for tick bite patients with neurological abnormalities. Public health workers and physicians should pay attention to neurological abnormalities caused by Rickettsia.

Rickettsia africae infection complicated with painful sacral syndrome in an Italian traveller returning from Zimbabwe.

We report a case of Rickettsia africae infection complicated with painful sacral syndrome in an Italian traveller returning from Zimbabwe. The patient presented with fever, a tache noire on the left leg, and a neurological syndrome characterized by severe pain of the left leg, predominantly located in the left dorsal thigh and radiating to the calf; she had urinary retention and faecal incontinence. The diagnosis of R. africae was confirmed by polymerase chain reaction on a skin biopsy. The severe left leg pain persisted despite a complete course of doxycycline. A 4-month course of corticosteroids and the addition of carbamazepine was needed to achieve the control of pain. This case highlights the possibility of severe manifestations of R. africae infection and the possibility of a complex pathogenesis of the neurological syndrome, due perhaps to both the direct damage induced by R. africae and an immune-mediated mechanism.

Visual loss associated with rickettsial disease.

UNLABELLED: Abstract Purpose: To characterize and analyze ocular involvement associated with visual loss in a cohort of patients with rickettsial disease. METHODS: Retrospective study of 16 eyes of 14 patients. RESULTS: Mean initial visual acuity (VA) was 20/63 (range, 20/800-20/25). White retinal lesions infiltrating inner retina was the most common finding occurring in 14 eyes (87.5%). It was associated with a serous retinal detachment (SRD), accurately detectable by optical coherence tomography, in 11 eyes (78.6%). Other findings included optic neuropathy in 7 eyes (43.75%), cystoid macular edema in 1 eye (6.25%), branch retinal artery occlusion in 1 eye (6.25%), and choroidal neovascularization in 1 eye (6.25%). Thirteen patients were treated with a 2-week course of oral doxycycline 200 mg/day. Mean final VA was 20/40. CONCLUSIONS: Inner retinitis, associated with mild vitritis and SRD, and optic neuropathy are the most common vision-threatening ocular manifestations of rickettsial disease.

Etiología y caracterización epidemiológica del síndrome febril no palúdico en tres municipios del Urabá antioqueño, Colombia / Etiology and epidemiological characterization of non-malarial febrile syndrome in three municipalities of Urabá (Antioquia), Colombia

Introducción. La región de Urabá es endémica para varias enfermedades febriles agudas de origen infeccioso. Sin embargo, solo los pacientes con malaria pueden acceder a un diagnóstico oportuno y rápido, motivo por el cual muchos síndromes febriles no palúdicos quedan sin diagnóstico etiológico claro. Objetivo. Establecer la etiología, describir las manifestaciones clínicas y explorar algunos posibles factores de riesgo relacionados con los síndromes febriles agudos no palúdicos en pacientes procedentes de los municipios de Necoclí, Turbo y Apartadó. Materiales y métodos. Se tomaron muestras de suero en fase aguda y de convalecencia de 220 pacientes febriles negativos para malaria, provenientes de zonas rurales y urbanas de Necoclí, Turbo y Apartadó en los años 2007 y 2008. Se practicaron pruebas para diagnóstico de dengue (detección de anticuerpos IgM por ELISA), leptospirosis (detección de anticuerpos IgM e IgG por IFI), rickettsiosis (detección de anticuerpos IgG por IFI), hantavirus y arenavirus (detección de anticuerpos IgG por ELISA). Resultados. Se encontraron frecuencias de dengue, leptospirosis, rickettsiosis y arenavirus de 37,3 %, 14,1 %, 2,7 % y 0,5 %, respectivamente. Se presentaron 12 casos de coinfección de leptospirosis-dengue y uno de leptospirosis-rickettsiosis-dengue. El sexo masculino y la humedad relativa media, fueron factores de riesgo para dengue. El inicio de signos clínicos en febrero de 2008, se asoció tanto con la infección por dengue como por leptospirosis. Conclusión. Se reafirma la importancia del virus del dengue, Rickettsia spp. y Leptospira spp., como agentes causantes del síndrome febril en la región del Urabá.

Introduction: Urabá, a region on the northern coast of Colombia, is endemic to several acute febrile illnesses of infectious origin; however, only patients with malaria may have access to quick and effective diagnosis. For this reason, many non-malarial febrile patients go without a clear etiologic diagnosis. Aim: To establish the etiology and clinical signs of acute febrile non-malaria syndromes and explore some of the likely risk factors in patients originating in the municipalities of Necocli, Turbo and Apartado who exhibit these symptoms. Materials and methods: We obtained acute and convalescent sera from 220 non-malarial febrile patients from the rural and urban zones of Necocli, Turbo and Apartado during 2007 and 2008. Serologic tests for dengue (IgM by ELISA), leptospirosis (IgM and IgG by IFA), rickettsiosis (IgG by IFI), hanta and arenavirus (IgG by ELISA) were performed. Results: We found that the frequency of infection for dengue, leptospirosis, rickettsiosis and arenavirus, was 37.3%; 14.1%; 2.7% and 0.5%, respectively. There were 12 co-infection cases of leptospirosis-dengue and one of leptospirosis-rickettsiosis-dengue. Male gender and relative humidity were considered risk factors for dengue, and the beginning of clinical signs in February of 2008 was associated with the infection of dengue and leptospirosis. Conclusion: This study confirms previous records that underline the importance of Rickettsia spp, dengue virus and Leptospira spp as causal agents of febrile syndrome in this region of Colombia.

Cutaneous leishmaniasis and rickettsial African tick-bite fever: a combination of exotic traveler's diseases in the same patient.

BACKGROUND: Cutaneous leishmaniasis and rickettsial African tick-bite fever are two zoonoses increasingly diagnosed in industrialized nations due to more international travel to endemic areas. METHODS: A 52-year-old American nurse was evaluated for a 0.5 cm well-demarcated, tender, shallow ulcer on her wrist, nonproductive cough, fever, chills, and night sweats, all of which began three weeks after travel to Botswana and a visit to a game reserve, where she reported being scratched on the ankle by a cheetah. RESULTS: This cutaneous finding was strongly suggestive of leishmaniasis, but the systemic symptoms were perplexing. Although excisional biopsy showed only nonspecific changes, a specimen sent to the United States Centers for Disease Control revealed leishmania promastigotes of L. tropica. Initial Rickettsia typhi titers and many other serologic tests were negative. However, four weeks after admission, R. typhi IgG titer was 1 : 64 and R. rickettsii IgG was 1 : 1024. CONCLUSION: Thus, our patient had two tropical diseases simultaneously.

Does a species of Rickettsia play a role in the pathophysiology of Buerger's disease?

Rickettsia is an intracellular pathogen that attaches to vascular endothelial cell membranes and its genome integrates into the DNA of the host and thereby inhibits apoptosis of the endothelial cells. Rickettsia can infect the body following a flea/louse bite. Rickettsia was suggested as one etiology of Buerger's disease long ago. We report a patient with Buerger's disease for whom a left below-knee amputation was done. Twenty-five biopsies for DNA extraction were obtained from the arteries, veins and microvasculature of the amputated limb. Three samples were positive for Rickettsia. The finding may explain the proliferation of endothelial cells in the pathology of Buerger's disease, segmental nature of the disease, involving small- and medium-sized vessels, and the prevalence of Buerger's disease among the low socioeconomic class of the society. Understanding the infectious etiology of Buerger's disease would be invaluable, since early antibiotic therapy or even vaccination might have prevented the limb loss in the current and other cases of Buerger's disease. The authors suggest that paraffin blocks of Buerger's disease biopsies be investigated for Rickettsia infection, focusing specifically on the area of endothelial cell proliferation for DNA extraction. These results should be compared with other biopsies from a variety of other peripheral vascular diseases.

Rickettsial infection with hemophagocytosis.

A five-year-old girl admitted with scrub typhus developed multiple organ dysfunction associated with hyperferritinaemia, hypofibrinogenaemia and hyperlipidaemia. Bone marrow aspiration studies confirmed haemophagocytic lymphohistiocytosis (HLH). HLH is a syndrome characterized by the uncontrolled activation and proliferation of macrophages and T-cells and can occur together with infections, connective tissue disorders, malignancies and genetic disorders.

Japanese spotted fever with acute hepatic failure: was it associated with Epstein-Barr virus?

BACKGROUND: An 81-year-old female experiencing high fever, fatigue, and loss of appetite was admitted to our hospital and diagnosed with acute cholecystitis. Her condition did not improve and an eschar and erythema subsequently appeared. We then diagnosed Japanese spotted fever (JSF). She recovered immediately after the administration of minocycline. This case differed from other cases because the patient had a remarkably acute hepatic failure. METHODS: Considering that the present case might be associated with other factors, we performed a repeat polymerase chain reaction (PCR) test on the patient's blood that had been collected on admission and stored. RESULTS: Epstein-Barr virus (EBV) was detected in her blood by PCR. CONCLUSION: We consider this case might be associated with EBV.

Nine cases of Japan spotted fever diagnosed at our hospital in 2008.

BACKGROUND: The diagnosis of Japan spotted fever (JSF) is very difficult in some cases. The initial diagnosis of JSF is very important to treat. METHODS: We report nine cases of Japan spotted fever (JSF) with variable clinical features diagnosed at our hospital in 2008. RESULTS: Concerning clinical symptom, the most frequent symptoms were fever (8/9) and erythema of the whole body (8/9), followed by eschar (4/9). Palmar erythema, vomiting, and headache were observed in two cases. Purpura and lymph node swelling were observed in one case. Complication with Disseminated intravascular coagulation (DIC) was observed in one case. Laboratory findings revealed elevated plasma level of C-reactive protein (CRP) and liver dysfunction in all cases, and decreased platelet (7/9). Interestingly, all patients had a history of presumed infection in the Southern area of Miya River, where wild Japanese deer with ticks (vector of Rickettsia japonica) may reside. CONCLUSION: Different procedures are performed to make a diagnosis of JSF. For an initial definite diagnosis and adequate treatment of JSF, PCR of samples taken from blood, and skin biopsy from erythema and eschar lesions are necessary. Paired serum to measure the titers of antibody against R. japonica is also important.

Causality in acute encephalitis: defining aetiologies.

Defining the causal relationship between a microbe and encephalitis is complex. Over 100 different infectious agents may cause encephalitis, often as one of the rarer manifestations of infection. The gold-standard techniques to detect causative infectious agents in encephalitis in life depend on the study of brain biopsy material; however, in most cases this is not possible. We present the UK perspective on aetiological case definitions for acute encephalitis and extend them to include immune-mediated causes. Expert opinion was primarily used and was supplemented by literature-based methods. Wide usage of these definitions will facilitate comparison between studies and result in a better understanding of the causes of this devastating condition. They provide a framework for regular review and updating as the knowledge base increases both clinically and through improvements in diagnostic methods. The importance of new and emerging pathogens as causes of encephalitis can be assessed against the principles laid out here.

A prospective study evaluating the presence of Rickettsia in Danish patients with sarcoidosis.

Rickettsia helvetica has previously been proposed as an aetiological agent in sarcoidosis. The purpose of the present study was to detect possible signs of Rickettsia infection in a Danish population of patients with sarcoidosis. Twenty-six patients with newly diagnosed sarcoidosis were prospectively enrolled in the study. The diagnosis was confirmed by biopsy in 18 and by clinical characteristics in 8 patients; 11 patients with different non-sarcoid lung diseases were recruited as controls. We obtained information regarding tick exposure and sarcoid disease manifestations by a structured interview. Evidence of rickettsial infection was assessed by an immunofluorescence assay testing for antibodies towards Rickettsia as well as specific real-time polymerase chain reaction (PCR) on lung biopsy specimens. We performed fluorescent in situ hybridization (FISH) on the biopsies to detect rickettsial and eubacterial rRNA. One sarcoidosis patient had serum rickettsial IgG antibodies above the chosen cut-off level. We found no positive rickettsial PCR or FISH analyses in any of the biopsy specimens. One sarcoid patient sample and 1 control sample contained unidentified bacteria. There was no difference in the reported frequency of tick bite between patients and controls. In conclusion, we found no evidence of Rickettsia being involved in the pathogenesis of sarcoidosis in Denmark.

Unusual pancytopenia secondary to haemophagocytosis syndrome in rickettsioses.

We report two patients who presented with a long-lasting febrile illness associated with pancytopenia. Both of them had evidence of hypercellular marrow with haemophagocytosis. They were confirmed as having rickettsial infections by serology and had a rapid haematological recovery with anti-rickettsial antibiotics. We highlight the importance of considering rickettsial infections in patients with such clinical presentations, especially in areas where these infections are endemic or re-emerging. Empirical use of anti-rickettsial antibiotics in such situations could be beneficial, when facilities to diagnose rickettsial diseases are not readily available.

Two cases of cellulitis in the course of African tick bite fever: a fortuitous association?

In African tick bite fever (ATBF), inoculation eschar - resulting from disruption of the cutaneous barrier - may be a risk factor for cellulitis. We report 2 cases of ATBF associated with cellulitis. A 77-year-old woman was referred for severe leg cellulitis upon returning from sub-Saharan Africa. She developed erythematous macules. Rickettsia africae was detected by PCR assay from a skin biopsy specimen, and ATBF diagnosis was confirmed. A 75-year-old man was hospitalized after his return from Zimbabwe for a maculopapular exanthema and erysipelas-like rash of the leg. The diagnosis of cellulitis associated with ATBF was confirmed by PCR and serological methods. Both patients were treated for ATBF and cellulitis by a combination of doxycycline and beta-lactam antibiotics, and both had a good recovery. Inoculation eschar may be a risk factor for cellulitis; thus, we hypothesize a non-fortuitous association between ATBF and cellulitis.