Hyperacute Form Research Articles

Acute disseminated encephalomyelitis as an emergency

Acute disseminated encephalomyelitis (ADEM) is a common acute multifocal autoimmune infl ammatory demyelinating disease of the central nervous system (CNS) with a predominant lesion of the white matter of the brain, brainstem and optic nerves, the conductors of the spinal cord, less often — gray matter of the CNS. ADEM is usually a self-limiting condition with spontaneous improvement and a favorable prognosis. Along with the possibility of a severe course in the classical form of ADEM, the development of hyperacute forms with a much more unfavorable prognosis is possible. Such variants of the course of ADEM are acute hemorrhagic leukoencephalitis (AHLE), acute hemorrhagic leukoencephalomyelitis and acute necrotizing hemorrhagic leukoencephalitis of Hurst, associated with the development of a cascade of hyperacute uncontrolled autoimmune reactions. The severity of these conditions (grouped under the term OHLE) is associated with rapid progression, brainstem involvement, large lesions is due to the development of acute edematous necrosis and hemorrhage with a high possibility of disability or death. The aggressive and severe course of АHLE requires the immediate initiation of decongestant and immunosuppressive therapy.

THELAZIOSIS IN WISENTS OF THE SHAHDAG NATIONAL PARK (AZERBAIJAN)

In the Shahdag National Park (Azerbaijan) the natural grouping of wisents (European bisons) is being formed. The program should eventually result in obtaining the independent stable grouping of wisents, capable of existing and reproduction without human interference. In the course of work with the grouping such a disease as wisent thelaziosis was detected. The presence of the disease can negatively affect the efficiency of the wisents reintroduction program. The aim of the work was to identify the problem, describe the clinical cases of wisent thelaziosis and determine possible measures to minimize risks for animals health. The article presents the data collected throughout a three years period of wisent group formation. The diagnosis – thelaziosis – was confirmed by finding the mature thelazia specimens of Thelazia rhodesi species. Such clinical manifestations as photophobia, eyelid edema, pathological lacrimation, serous conjunctivitis, purulent-catarrhal keratoconjunctivitis, clouding and ulceration of the cornea up to perforating ulcers, iridocyclitis were observed in wisents. The clinical form of thelaziosis had been detected in a wisent herd at all seasons of the year, at maximum in the period from the end of May to the end of July, up to 18.8 % of animals in the herd. At the rest of the time, the percentage of animals with disease manifestation varied from 3.7 to 11 %; two years in a row the cases of disease manifestation in adult wisents were observed in February. One case of thelaziosis was registered in a 1.5-month-old calf, the disease evolved in a hyperacute form. For treatment against thelaziosis in wisents the single intramuscular injections of ivermectin at a dose of 200 μg/kg (Ivermec, 2 ml/100 kg) were used. Medical treatment was given frontally to the herd after each detected clinical case. In addition wisents with strongly expressed clinical signs received a single injection of tulathromycin at a dose of 2.5 mg/1 kg (Draxin, 2.5 ml/100 kg). Medications were injected by means of a remote gun Dan-Inject. In Azerbaijan thelaziosis is spread among productive animals, as evidenced by veterinary reports. However, systematic studies of thelaziosis were carried out only in the 70–80s. As follows from the studies the thelaziosis infection rate in Azerbaijan has clearly expressed zonal distribution: high infection rate in the plain and submontane zones and rare cases of disease occurrence in the mountain belt. It was concluded that when forming wisents population, it is necessary to take into account the factor of zonality and plan the populations’ release in the mountainous areas of the national park, as the safest from veterinary side. Also due to domestic animals being the main source of infection for wisents in Azerbaijan, it is necessary to conduct research on disease expansion and intensity of infection in domestic livestock in the areas bordering with the Shahdag National Park. Currently while wisents are kept at the quarantine and transfer place, given the proximity of the enzootic focus, it is recommended to conduct the systematic frontal preventive treatment with ivermectin.

061 Immunohistochemical study of the PD-1/PD-L1 pathway in cutaneous lupus erythematosus

The pathomechanism of various autoimmune diseases is known to be associated with the altered function of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) axis. We aimed to investigate the role of this pathway and inflammatory cell markers in subtypes of cutaneous lupus erythematosus (CLE): discoid lupus erythematosus (DLE), subacute CLE (SCLE) and toxic epidermal necrolysis (TEN)-like lupus, a hyperacute form of acute CLE (ACLE). Ten skin biopsy samples from 9 patients were analyzed with immunohistochemistry regarding the following markers: CD3, CD4, CD8, Granzyme B, CD123, CD163, PD-1, PD-L1.

Review Onepidemiology of Contagious Bovine Pleuoro Pneumonia and Its Economic Impacts in Ethiopia

Mycoplasma Mycoides subsp. Mycoides “Small Colony” (MmmSC) causes the infectious and contagious respiratory disease known as Contagious Bovine Pleuropneumonia (CBPP), which has a significant negative effect on livestock output and the propensity to spread quickly. The aim of this paper is to review the epidemiology and economic impacts of CBPP in Ethiopia. Contagious Bovine pleuropneumonia is an endemic disease in Africa, Asia, Eastern Europe, and the Iberian Peninsula. Contagious Bovine pleuropneumonia is mainly transmitted from animal to animal in respiratory aerosols. The clinical manifestations of CBPP in cattle range from hyper acute, acute, sub acute and chronic forms. Diagnosis CBPP based on a history of contact with infected animals, clinical findings, Immuno-diagnosis tests, necropsy findings and cultural examination. Thrombosis in the pulmonary arteries is a hallmark of the CBPP pathogenesis in susceptible animals. The impact that Contagious Bovine Pleuropneumonia (CBPP) can impart in an economy of a given country is so vast and tremendous that it is not advisable to overlook like any of the ordinary routine diseases of livestock that can be easily removed by treatment or self-cure. Movement control, vaccination, and treatment are essential tools in CBPP control and eradication. Regular program of mass vaccination and best treatment regime. Moreover, effective vaccination policy needs to be considered as it is the only realistic method of choice for control of CBPP in Ethiopia.

Immunohistochemical Study of the PD-1/PD-L1 Pathway in Cutaneous Lupus Erythematosus.

The pathomechanism of various autoimmune diseases is known to be associated with the altered function of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) axis. We aimed to investigate the role of this pathway and inflammatory cell markers in subtypes of cutaneous lupus erythematosus (CLE): discoid lupus erythematosus (DLE), subacute CLE (SCLE) and toxic epidermal necrolysis (TEN)-like lupus, a hyperacute form of acute CLE (ACLE). Ten skin biopsy samples from 9 patients were analyzed with immunohistochemistry regarding the following markers: CD3, CD4, CD8, Granzyme B, CD123, CD163, PD-1, PD-L1. Our group consisted of 4 SCLE (2 idiopathic (I-SCLE) and 2 PD-1 inhibitor-induced (DI-SCLE)), 4 DLE and 1 TEN-like lupus cases. From the latter patient two consecutive biopsies were obtained 1 week apart. Marker expression patterns were compared through descriptive analysis. Higher median keratinocyte (KC) PD-L1 expression was observed in the SCLE group compared to the DLE group (65% and 5%, respectively). Medians of dermal CD4, Granzyme B (GB), PD-1 positive cell numbers and GB+/CD8+ ratio were higher in the DLE group than in the SCLE group. The I-SCLE and DI-SCLE cases showed many similarities, however KC PD-L1 expression and dermal GB positive cell number was higher in the former. The consecutive samples of the TEN-like lupus patient showed an increase by time within the number of infiltrating GB+ cytotoxic T-cells and KC PD-L1 expression (from 22 to 43 and 30%–70%, respectively). Alterations of the PD-1/PD-L1 axis seems to play a role in the pathogenesis of CLE.

Evaluation of the sensitivity of the classical swine fever surveillance system in two free zones in Colombia.

Infection with the classical swine fever virus (CSFV) causes a disease in pigs that ranges from a hyperacute form in which animals die in a few hours to subclinical disease. Due to this wide range of virulence, several complementary surveillance strategies should be implemented for the early detection of the disease. The objective of the present study was to determine the sensitivity of the surveillance system to detect CSFV outbreaks in a free zone (Zone 1) and in a zone undergoing an eradication process (Zone 2) in Colombia. Stochastic scenario tree models were used to describe the population and surveillance structures and to determine the probability of CSFV detection. The total sensitivity of the surveillance system in the case of a single infected farm in Zone 1 was 31.4% (CI 95%: 7.2-54.1) and in the case of 5 infected farms was 85.2% (CI 95%: 67.3-93.7), while in Zone 2 the sensitivities were 27.8% (CI 95%: 6.4-55.1) and 82.5% (CI 95%: 65-92.9), respectively. The on-farm passive surveillance shows the highest sensitivity for detection of a single CSFV infected farm in both zones (22.8% in Zone 1 and 22.5% in Zone 2). The probability of detection was higher in a family / backyard premise than on a commercial farm in both zones. The passive surveillance at slaughterhouse had a sensitivity of 5.3% and 4.5% for the detection of a single infected farm in Zone 1 and 2, respectively. Active surveillance presented a range of sensitivity between 2.2% and 4.5%. In conclusion, the sensitivity of the surveillance in the two studied zones was quite high, one of reasons for this good sensitivity being the sentinel network based on the voluntary participation of 5,500 collaborators that were trained for the identification and notification of diseases of national interest.

Association of acute disseminated encephalomyelitis (ADEM) and COVID-19 in a pediatric patient.

Cases of acute disseminated encephalomyelitis (ADEM) and its hyperacute form, acute hemorrhagic leukoencephalitis (AHLE), have been reported in coronavirus disease 2019 (COVID-19) patients as rare, but most severe neurological complications. However, histopathologic evaluations of ADEM/AHLE pathology in COVID patients are extremely limited, so far having only been reported in a few adult autopsy cases. Here we compare the findings with an ADEM-like pathology in a pediatric patient taken through a biopsy procedure. Understanding the neuropathology may shed informative light on the autoimmune process affecting COVID-19 patients and provide critical information to guide the clinical management.

Hyper-Acute Presentation of Access Based Cardiac Disease

Fifty years after the creation of the first arteriovenous access, little is known about the deleterious cardiac effects of this pathological circuit. Understanding the pathophysiology of Access Based Cardiac Disease (ABCD) is critical, given the fact that cardiac abnormalities are the leading cause of morbidity and mortality in end stage kidney disease patients on dialysis. However, this has been a challenge, as many of hemodialysis patients have preexisting cardiac disease, they invariably have volume overload from salt and water retention, and many heart failure symptoms can be masked by regular efficient dialysis. ABCD can be hyper-acute (minutes to hours), acute (days to weeks), or chronic (months to years). In this manuscript, authors will focus on the hyper-acute form.

Erysipelas, the opportunistic zoonotic disease: history, epidemiology, pathology, and diagnosis—a review

Due to the recent multidisciplinary collaborations towards ‘One Health’, it was necessary to review this important zoonotic disease, erysipelas. Swine erysipelas also referred to as diamond skin disease has since become one of the most serious hazards of swine production worldwide. Erysipelothrix rhusiopathiae, the aetiology of erysipelas could affect pigs, turkeys, sheep, chickens, ducks, and emus. The most important animal reservoir of E. rhusiopathiae is the domestic swine. The organism is shed by diseased animals in faeces, urine, saliva, and nasal secretions, which can contaminate food, water, and soil. Swine erysipelas is made up of the hyperacute form, the septicaemia, and cutaneous (diamond) forms (acute), and the chronic form, characterised in pigs by joint lesions (arthritis), vegetative endocarditis, alopecia, and dermatitis. These signs are accompanied by poor fertility, increased prevalence of abortions, stillbirths, and small litter size. Reports of human cases are related to occupational exposure placing fishermen, butchers, slaughterhouse workers, veterinarians, housewives, poultry industry workers, and other agricultural based workers at higher risk. Diagnosis of erysipelas is based on clinical signs, gross lesions, response to antimicrobial therapy, and demonstration of the bacterium using bacterial culturing, mouse protection test, microscopy and mass spectrometry or demonstration of bacterial DNA in tissues from affected animals using PCR assays, immunohistochemical methods, and other serological methods. Swine erysipelas as an opportunistic zoonotic disease is on the increase hence, a synergistic effort should be garnered towards reducing the negative influence of this disease, through enhanced awareness of this disease amongst farmers, butchers, housewives, veterinarians, and drug researchers.

Canine babesiosis

The causative agents of canine babesiosis are Babesia canis and B. gibsoni which are transmitted by various hard tick species and blood transfusions. In the hyperacute form of the disease hypothermia, shock, severe metabolic acidosis and disseminated intravascular coagulation usually precede the death of the dog occuring in less than 24 hours. Severe anemia, icterus, splenomegaly and peripheral lymphadenopathy characterize the acute form of the disease. Intermittent fever and progressive loss of body weight may be noticed in the chronic form of babesiosis, while its many atypical clinical manifestations (e.g. ascites, gastrointestinal signs, CNS disease, subcutaneous edema, masticatory myositis) often cause diagnostic confusion. The organism detection on RBC in thin blood smears made from the buffy coat is a must for definitive diagnosis. The IFA test is a good choice for screening large numbers of dogs for detecting the asymptomatic carriers. Complete parasitological cure can be obtained with imidocarb dipropionate, pentamidine isethionate or diminazene aceturate, while metronidazole and clindamycin have been recently suggested as good alternatives. Supportive care is considered crucial for the survival of the severely affected animals. While effective tick control is the mainstay of prevention, doxycycline and imidocarb may also play a significant role to that goal. The effectiveness of a killed vaccine is still a matter of controversy.

Commentary: Acute Hemorrhagic Leukoencephalitis (Weston-Hurst Syndrome) in a Patient with Relapse-Remitting Multiple Sclerosis.

Recently, Yildiz et al. reported the occurrence of acute hemorrhagic leukoencephalitis (AHLE) in a patient with pluriannual relapse-remitting multiple sclerosis (MS) after 1 month of high-dose interferon-β-1a treatment. The authors raised the question whether this case may be a hyperacute form of acute disseminated encephalomyelitis (ADEM) or a rare hemorrhagic evolution of tumefactive demyelination (TD), both unusual in the course of MS (1). They concluded that AHLE occurrence was unrelated to the underlying MS since hemorrhage has not been found in neuropathological patterns of both MS and TD. Although two published case reports of TD with hemorrhage in the course of fingolimod and natalizumab therapies (brain biopsy was not performed) have been mentioned in the paper, the potential predisposing effect of interferon-β therapy on the AHLE development has not been hypothesized.

Evolución clínica de la forma hiperaguda de la encefalomielitis aguda desmielinizante

IntroductionAcute disseminated encephalomyelitis (ADEM) is an inflammatory disease that damages the white matter of the central nervous system. Its clinical course is monophasic and multifocal. The outcome is usually favourable. We report our experience in the management of the hyperacute form of ADEM. Patients and methodsA retrospective chart review was performed on five patients admitted in coma with a diagnosis of ADEM in the Paediatric Intensive Care Unit (PICU). We describe their epidemiological, clinical, microbiological, magnetic resonance imaging features and their treatment and outcomes. ResultsThe mean age was 5.2 years and all were male. None of them fulfilled radiologic criteria for acute haemorrhagic leukoencephalitis. At admission all patients were in a coma, and all were on controlled mechanical ventilation support. Before their admission all patients had fever. In all cases the time between the first neurological symptom and coma was ≤ 24hours. The cerebrospinal fluid examination was abnormal in three patients, and in one case, oligoclonal bands were detected. The first brain magnetic resonance imaging (MRI) showed white matter and basal ganglia lesions in all patients, and in three cases the spinal medulla was affected by demyelination. All patients were treated with a course of high-dose methylprednisolone. Four patients were also treated with high-dose immunoglobulins, and one of them received plasmapheresis. Two patients died, and one patient had severe sequelae at discharge from the PICU. At discharge the lesions in the white matter were still present in the MRI. After nine months the three survivors had a Glasgow Outcome Scale score of five and no one relapsed. ConclusionsThere is a hyperacute clinical form of ADEM which has a high mortality rate. In the short term, the clinical improvement of hyperacute ADEM is not accompanied by a decrease of severity of the brain MRI.

Recent Epidemic-Like Anthrax Outbreaks in Italy: What Are the Probable Causes?

In Italy, in an area of about 50 km2 between Basilicata and Campania Southern regions, 28 outbreaks of anthrax occurred from August 28th to September 27th 2011. Different species were affected: laboratory tests confirmed anthrax in cattle, horses and sheep. The genetic analysis of strains isolated from infected animals indicated that outbreaks occurring in the two regions were not correlated. Intriguingly, the incidence was highly significant in horses compared to that of cattle and sheep or goats, which were prevalent species in the animal population. In addition, allinfected horses and many cattle developed a fatal, sub-acute form of anthrax, characterized by the presence of massive edema, usually absent in hyperacute forms. The characteristics of these outbreaks suggested a possible role of tabanids as vectors in the transmission of B. anthracis like-epidemic infection.

Fatal Mycoplasma Pneumoniae Infection: Case Report and Review of the Literature

BMycoplasma pneumoniae (M. pneumoniae) infection is rarely fatal in young adults. Most patients have no symptoms or mild nonspecific symptoms or signs with infection. Up to 310% infected people may develop pneumonia. We herein report a fatal case of M. pneumoniae infection presenting with acute respiratory failure and brain death in a 27 year old female. Autopsy revealed that diffuse alveolar damage in the lungs and acute hemorrhagic leukoencephalopathy (AHLE), a hyperacute form of acute disseminated encephalomyelitis (ADEM) in the brain. [N A J Med Sci. 2012;5(2):126-130.]

It is still not for the old iron: adjuvant effects of carbonyl iron in experimental autoimmune encephalomyelitis induction

Experimental autoimmune encephalomyelitis (EAE) is a model of multiple sclerosis. Dark Agouti rats immunized with spinal cord homogenate (SCH) and carbonyl iron (CI), as an adjuvant, develop severe hyperacute form of EAE. They succumb to EAE earlier and have higher clinical scores and lethality rate in comparison to counterparts immunized with SCH + complete Freund's adjuvant. There is no difference in the number of cells or in histological presentation of the CNS infiltrates of rats immunized with the two adjuvants. However, there are more granulocytes, NK and NKT cells, and less CD4(+) T cells in the spinal cord infiltrates of SCH + CI-immunized animals. Nitric oxide (NO)-generating enzyme inducible NO synthase have higher expression in spinal cord of SCH + CI-immunized rats, and this corresponds to more intensive nitrotyrosine formation in the CNS tissue of these rats. Abundant infiltration of granulocytes and NK cells into the CNS and excessive generation of peroxynitrite within the CNS of SCH + CI-immunized rats might account for the severe neurological deficits induced by immunization with CI. These factors should be closely examined in the fulminant forms of multiple sclerosis and acute disseminated encephalomyelitis, as they could represent a promising targets for therapy.

Acute Hemorrhagic Leukoencephalitis

Acute hemorrhagic leukoencephalopathy (AHLE) is a rare, acute disorder characterized by perivenular demyelination and diffuse hemorrhagic necrosis of the central nervous system. AHLE is thought to represent a hyperacute form of acute disseminated encephalomyelitis. AHLE is associated with a greater morbidity and mortality and, fortunately, is much less common than acute disseminated encephalomyelitis. Since most cases of AHLE result in patient demise, forensic pathologists should be cognizant of this entity and consider it in their differential diagnosis.Here we describe an interesting case of a previously healthy 11-year-old boy who initially complained of vague gastroenteritis-like symptoms while visiting a mountain lake. The boy's symptoms evolved to include severe headache and dizziness, necessitating a visit to a rural emergency department. He presented with focal neurologic findings, and head computed tomography (CT) scan confirmed thalamic edema. Cerebrospinal fluid analysis was suggestive of infectious etiology, and multiple empiric therapies were initiated. He was transferred to our institution, and his clinical status continued to worsen. Given the poor prognosis, the family requested withdrawal of supportive care. On day 14 of symptoms the boy succumbed to his illness. An autopsy was requested to further characterize the proximate cause of death.AHLE often presents with abrupt onset of fever, neck stiffness, seizure, and/or focal neurologic signs several days following a viral illness or vaccination. Thus, AHLE can clinically mimic a direct central nervous system infection or a toxic ingestion. AHLE has a very poor prognosis, with rapid deterioration and death usually occurring within days to one week after onset of symptoms. The cause for AHLE is unclear. An autoimmune pathophysiology is likely, with immune cross-reactivity between myelin basic protein moieties and various infectious agent antigens. Treatment for AHLE is not well-established; some authors describe in recent literature that a combination of immunosuppressant medications and/or therapeutic plasma exchange may be of benefit in treating AHLE.

Treatment of Severe Acute Graft-Versus-Host Disease with Mesenchymal Stromal Cells.

Abstract 2249Poster Board II-226 BACKGROUND.Allogeneic hematopoietic stem cell transplantation (HSCT) is being used to treat a range malignant and nonmalignant conditions. However, it often causes potentially lethal Graft-versus-Host Disease (GVHD). Several studies revealed that mesenchymal stromal cells (MSCs) from human bone marrow can down regulate GVHD after HSCT. METHODS.MSCs were obtained from BM, expanded and characterized by their morphology, immunophenotype, immunosuppressive potential for autologous, partially and fully mismatched lymphocytes. Twenty five patients (pts) got 39 (range, 1 to 4) MSCs infusions for 27 episodes of acute GVHD, which was defined as steroid resistant grade IV aGVHD in all but one patient. RESULTS.GvHD characteristics. Acute GVHD started from day +6 to d +46 from HSCT (median d+18) excluding single pt in whom it occurred on d+150. In 2 pts disease manifested in a hyper acute form before the engraftment (on d+6 and d+8, respectively). In all but one pt GI GVHD was defined as grade IV with full clinical picture of it. Skin GVHD accompanied GI symptoms in 17 pts and 13 was > grade II, in 4 grade IV. Liver symptoms presented in 13 pts, one pt was determinate as VOD. In 3 pts liver involvement was defined as grade IV. In all 24 of 25 pts had GVHD grade IV 4 and one grade III. Previous conventional anti GVHD therapies included: MP in all pts, MTX, various calcineurin inhibitors, MMF, ECP, serotherapy. Only 3 pts showed temporary limited partial response.Treatment with MSCs. The 1st infusion with MSC was given on day +32.5 (range, 8 to 74); d+50 (range, +28 to +180) post diagnosis of aGVHD and HSCT HSCT, respectively. In 22 evaluable pts we treated 24 separate episodes of GVHD: 22 first episodes and in 2 pts relapse of GVHD. In 24 of 39 cases treatment was performed with frozen MSC and in 15 with fresh cultured cells. In 37/39 cases passages 1 to 3 were used. Median number of infused cells was 1 (range, 0.3 to 3.1) x10 6 per kg of pt body weight in each treatment. Initial response was seen in 17/24 episodes of aGVHD (70.8%), in 8 partial (PR) and in 9 complete (CR). Two pts experienced GVHD relapse after achieving CR and very good PR: one case was treated successfully while another was resistant to MSCs. The latest pt with grade IV aggressive liver GVHD received MSCs injections intra hepatic arteries under radiological control following IRB approval with no anti GVHD effect. The procedure was uneventful with no evidence of microembolisation, no changes of blood flow or deterioration of liver tests (cytolysis). We observed a trend for better effect with higher MSC cell dose: total and per first infusion MSCs dose (1.93±1.28 vs. 1.23±0.50, p=0.078; 1.28±0.79 vs. 0.88±0.28, p=0.086). In all cases effect was seen after the first procedure. No difference was noted in the anti GVHD activity between fresh vs. frozen MSCs. There were no immediate or late toxicity or side effects.Overall survival. 14/25 patients are alive up to 20 months follow up. 8/11 pts, died from GVHD (4 within 1-10 d from MSCs infusion), and 3 from other unrelated causes including TTP-1, DAH-1 and disease progression-1. CONCLUSION.Treatment with MSCs seems to be a new novel type of therapy for steroids resistant GVHD with promising preliminary results and low toxicity. Obviously multicenter 2 arm randomized study is in need to confirm these encouraging. Disclosures:No relevant conflicts of interest to declare.

Acute Hemorrhagic Leukoencephalitis in a Patient with Sickle Cell Disease: A Case Report

Acute hemorrhagic leukoencephalitis (AHLE), otherwise known as Hurst’s Disease, is a rare, rapidly progressive and usually fatal demyelinating condition affecting the central nervous system. It is usually preceded by an upper respiratory tract infection and is thought by many authors to be a hyperacute form of post infectious encephalomyelitis. It was recently found to be linked to Epstein-Barr virus infection. We report what we think is the first case of AHLE occurring in a child with homozygous sickle cell disease. As with our case, this is usually a fatal condition; however, there have been few recent reports of survival following aggressive, high dose corticosteroid therapy. It is therefore important to recognize this disease early so appropriate treatment can be instituted. Work done in the Department of Pathology, University Hospital of the West Indies, Kingston, Jamaica WI

Acute sensory neuronopathy as the presenting symptom of Sjögren’s syndrome

Sensory neuronopathy associated with Sjögren’s syndrome (SS) usually has a subacute or chronic onset. We report the case of a 37-year-old woman who presented with an unusual hyperacute form of SS ganglionopathy. She initially developed paresthesias of her fingertips and rapidly became severely ataxic. Nerve conduction studies revealed abnormal sensory but normal motor functions. Lip biopsy showed findings consistent with SS. Sural nerve biopsy showed severe axonal loss. The patient showed modest improvement with immunosuppressive therapies.

The Clinical Spectrum of Acute GVHD: Beyond Day 100.

Objective: To assess the clinical and prognostic implications of the timing of acute GVHD (aGVHD).Introduction: Traditionally, the syndrome of acute GVHD has been chronologically defined as GVHD occurring before day 100. It has become increasingly clear that this syndrome can occur after day 100, which raises the question of historical misclassification of aGVHD occurring after day 100 (“late aGVHD”) as chronic GVHD. On the other hand, timing of GVHD could have prognostic implications and the case in hyperacute forms of GVHD are an example. In this study, we redifine aGVHD based on clinical manifestations and we evaluate risk factors as well as clinical and prognostic differences between late aGVHD and GVHD before day 100 (“classic aGVHD”).Methods: Retrospective evaluation of records and database on all matched sibling transplants (n= 128) performed at UT MDACC from 1/00 to 2/02.Results: A total of 47 patients (37%) had “classic” aGVHD and another 67 (52%) were classified as chronic GVHD (cGVHD) in our database. Upon review of medical records, 30/67 patients (45%) were found to have late aGVHD, and the remainder true cGVHD. Of these 30 patients, 9 had aGVHD progressing through day 100 and were reclassified as classic aGVHD. The remainder 21 had newly diagnosed late aGVHD. We evaluated risk factors for developing late aGVHD in patients who were alive at day 100. Only a later engraftment (ANC>500 beyond day 12) was associated with a higher incidence of late aGVHD, while age, gender, malignancy, disease status at transplant, type of preparative regimen (nonmyeloablative versus others), bone marrow vs peripheral blood or CD3,4 or 8 infused did not impact the incidence of late acute GVHD. Compared to classic aGVHD, the late group had a significantly higher proportion of grade 2–4 GVHD (85 vs 61%, p= 0.03) with similar grade 3–4 aGVHD (29 vs 27%, p= 0.5). Skin and GI involvement, as well as isolated elevation of the alkaline phosphatase were more common manifestations of late aGVHD. There was a trend to better response (CR/PR) to first line immunosuppression in patients with late aGVHD (81 vs 63%, p= 0.13), but this was not statistically significant. The overall survival (OS) and non-relapse mortality (NRM) since the diagnosis of GVHD were substantially better in patients with late aGVHD (OS 70 vs 29%, p= 0.01; NRM 16 vs 39%, p= 0.06). Finally, the NRM of patients with chronic GVHD prior to reclassifying patients with late aGVHD (n= 67) was 28% at 2 years. When patients with late aGVHD were excluded, the NRM at 2 years for the remainder 37 patients with chronic GVHD was 20% (p= 0.3).Conclusions: 1- The current chronological definition of acute GVHD may lead to misclassification of late aGVHD as chronic GVHD. This could have implications in interpreting the current knowledge and literature on GVHD, 2- There was a trend to higher NRM in the chronic GVHD group prior to reclassifying cases of late aGVHD, althought the difference was not statistically significant, 3-Patients with late aGVHD share similarities with those with classic aGVHD, although there seems to be a trend to better response to therapy and better survival in patients developing aGVHD beyond day 100. Thus, timing of aGVHD may affect its outcome.