ABSTRACT
Introduction/Background: Antiphospholipid syndrome (APS) is a rare autoimmune multisystem disease characterised by thrombosis and pregnancy morbidity in the presence of persistently elevated titres of: lupus anticoagulant, anticardiolipin and/or anti-glycoprotein 1. It may be primary (occurring alone) or secondary (in combination with another disease, most commonly systemic lupus erythematosus (SLE)). Recent publications highlighted clinical criteria limitations for children and raised awareness of the burden and prevalence of non-criteria manifestations in this population. This case report adds further weight to the need to raise multi-specialty awareness of non-criteria manifestations to aid recognition and treatment of this rare condition with potentially severe sequelae. Description/Method: 13-year-old female with SLE diagnosed aged 8 in India with bilateral optic neuritis occurring two months later. ANA positive at diagnosis with low complement and thrombocytopenia. Treated with prednisolone and hydroxychloroquine. Patient moved to the UK aged 9;initial abnormal bloods: mildly positive ANA (ENA negative), thrombocytopenia, strong lupus anticoagulant. As serology not strongly suggestive and optic neuritis rare in lupus diagnosis questioned. Ophthalmology review confirmed bilateral optic atrophy without evidence of previous vasculitis. There was debate whether the postretinal demyelination was due to antiphospholipid syndrome or a primary demyelinating condition. Hydroxychloroquine stopped and azathioprine started. Following normal neurology investigations (brain, spine MRI/MRV/MRA) concluded if patient developed new APSrelated symptoms or worsening visual evoked potentials anticoagulation would be discussed. Patient remained stable over four years with chronic thrombocytopenia and ESR persistently elevated. Azathioprine changed to Mycophenolate mofetil (MMF) due to side effects. Routine medication monitoring bloods in 2022 showed ESR 97, CRP 78, Platelets 61. Review identified vasculitic rash on soles of both feet with palpable nodules and normal pulses. Further investigation confirmed antiphospholipid antibody triple positivity. Aspirin commenced, hydroxychloroquine restarted, MMF dose increased and rituximab administered. Left foot rash settled but right progressed with toe discolouration and numbness. Skin biopsy considered but not performed due to skin integrity concerns. Foot pulses remained present and normal. Bilateral lower limb doppler reported as normal;increased symptoms resulted in CT angiogram which revealed bilateral non-occlusive popliteal thrombus and left pulmonary embolus. Subsequent echocardiogram was normal. Patient was anticoagulated with low molecular weight heparin followed by warfarin. Vascular surgical team advocated medical management and patient received seven infusions of Iloprost followed by Sildenafil. She achieved near total resolution of skin changes to toes with only minimal loss of skin over tip of right great toe. Patient will now require long-termanticoagulation. Discussion/Results: APS was considered in initial differential diagnosis but patient did not meet current clinical criteria as no past evidence of thrombosis. Lupus anticoagulant was consistently strongly positive and anticardiolipin repeatedly negative. As anti-B2 glycoprotein 1 antibody is not routinely tested and must be verbally requested, it was only checked once (negative) prior to discovery of triple positivity. ANA reported as strongly positive at time of SLE diagnosis but reviewing original notes from India titre was 1:100 and therefore not highly convincing. ENA negative and complement and white cell count normal on repeat testing since. Therefore, it is probable that this patient has primary APS as opposed to secondary APS in association with SLE. However, it is possible that this patient may develop more symptoms of SLE over time. When this patient presented with foot rash there were high numbers of children presenting with varying severity of painful, itchy toes coined 'covid toes' due to suspected lin to SARS-CoV-2 infection. Patient had exposure history, and COVID antibody serology was difficult to interpret due to recent vaccination. Dermatology found appearance to be consistent with 'covid toes' and advised supportive treatment. The triple APS antibody positivity result provided probable aetiology. Providing evidence of thrombus was problematic with false reassurance from apparently normal lower limb arterial doppler when actually popliteal arteries were not checked in view of the presence of normal flow proximally at the groin and distally in the feet. This case highlights the need to continue to search for thrombus in presence of high titres antiphospholipid antibodies and particularly in the case of triple positivity as although patient presented with colour change to toes, she was entirely asymptomatic from her PE and her left foot improved spontaneously despite a left popliteal thrombus also being present. Key learning points/Conclusion: Non-criteria manifestation of thrombocytopenia (occurs in 25% paediatric APS patients) was present throughout and patient had past history of haematuria (a recognised renal non-criteria manifestation). A paediatric specific APS criteria including these may have resulted in earlier detection of triple antiphospholipid antibody positivity and thus earlier treatment escalation and possible avoidance of thrombus. It has been reported that a high proportion of children with positive antiphospholipid antibodies don't develop a thrombus. However, it is interesting that our patient was entirely asymptomatic from her pulmonary embolus which was an incidental finding on her CT angiogram. This prompts a discussion about how much imaging should be performed in those with high levels of persistent positive antiphospholipid antibodies. Rituximab resulted in normalisation of platelet count and ESR for the first time since initial presentation. Anticardiolipin antibodies normalised, lupus anticoagulant decreased from strong to moderate and anti- B2 glycoprotein levels decreased but remained positive. Rituximab is a recognised treatment for catastrophic antiphospholipid syndrome (CAPS) but not routinely used in APS. The consistently raised ESR in an apparently clinically well patient is a reminder to continue to search for causes of inflammation. As the CRP was largely in normal range, this demonstrates the unique value of the ESR. In view of anti-B2 glycoprotein 1 antibody requiring to be verbally requested, discussions are ongoing with the laboratory department regarding the possibility of electronic request and a comment with recommendation to check other two antiphospholipid antibodies following one positive antibody result. As a result of this case, a plan will be put in place to ensure annual screening of antiphospholipid antibodies in all juvenile SLE patients in our care. It is hoped that this case report promotes discussion amongst the paediatric rheumatology community regarding further research required for development of paediatric specific APS criteria and management.
ABSTRACT
Introduction/Background: Antiphospholipid syndrome (APS) is a rare autoimmune multisystem disease characterised by thrombosis and pregnancy morbidity in the presence of persistently elevated titres of: lupus anticoagulant, anticardiolipin and/or anti-glycoprotein 1. It may be primary (occurring alone) or secondary (in combination with another disease, most commonly systemic lupus erythematosus (SLE)). Recent publications highlighted clinical criteria limitations for children and raised awareness of the burden and prevalence of non-criteria manifestations in this population. This case report adds further weight to the need to raise multi-specialty awareness of non-criteria manifestations to aid recognition and treatment of this rare condition with potentially severe sequelae. Description/Method: 13-year-old female with SLE diagnosed aged 8 in India with bilateral optic neuritis occurring two months later. ANA positive at diagnosis with low complement and thrombocytopenia. Treated with prednisolone and hydroxychloroquine. Patient moved to the UK aged 9;initial abnormal bloods: mildly positive ANA (ENA negative), thrombocytopenia, strong lupus anticoagulant. As serology not strongly suggestive and optic neuritis rare in lupus diagnosis questioned. Ophthalmology review confirmed bilateral optic atrophy without evidence of previous vasculitis. There was debate whether the postretinal demyelination was due to antiphospholipid syndrome or a primary demyelinating condition. Hydroxychloroquine stopped and azathioprine started. Following normal neurology investigations (brain, spine MRI/MRV/MRA) concluded if patient developed new APSrelated symptoms or worsening visual evoked potentials anticoagulation would be discussed. Patient remained stable over four years with chronic thrombocytopenia and ESR persistently elevated. Azathioprine changed to Mycophenolate mofetil (MMF) due to side effects. Routine medication monitoring bloods in 2022 showed ESR 97, CRP 78, Platelets 61. Review identified vasculitic rash on soles of both feet with palpable nodules and normal pulses. Further investigation confirmed antiphospholipid antibody triple positivity. Aspirin commenced, hydroxychloroquine restarted, MMF dose increased and rituximab administered. Left foot rash settled but right progressed with toe discolouration and numbness. Skin biopsy considered but not performed due to skin integrity concerns. Foot pulses remained present and normal. Bilateral lower limb doppler reported as normal;increased symptoms resulted in CT angiogram which revealed bilateral non-occlusive popliteal thrombus and left pulmonary embolus. Subsequent echocardiogram was normal. Patient was anticoagulated with low molecular weight heparin followed by warfarin. Vascular surgical team advocated medical management and patient received seven infusions of Iloprost followed by Sildenafil. She achieved near total resolution of skin changes to toes with only minimal loss of skin over tip of right great toe. Patient will now require long-termanticoagulation. Discussion/Results: APS was considered in initial differential diagnosis but patient did not meet current clinical criteria as no past evidence of thrombosis. Lupus anticoagulant was consistently strongly positive and anticardiolipin repeatedly negative. As anti-B2 glycoprotein 1 antibody is not routinely tested and must be verbally requested, it was only checked once (negative) prior to discovery of triple positivity. ANA reported as strongly positive at time of SLE diagnosis but reviewing original notes from India titre was 1:100 and therefore not highly convincing. ENA negative and complement and white cell count normal on repeat testing since. Therefore, it is probable that this patient has primary APS as opposed to secondary APS in association with SLE. However, it is possible that this patient may develop more symptoms of SLE over time. When this patient presented with foot rash there were high numbers of children presenting with varying severity of painful, itchy toes coined 'covid toes' due to suspected lin to SARS-CoV-2 infection. Patient had exposure history, and COVID antibody serology was difficult to interpret due to recent vaccination. Dermatology found appearance to be consistent with 'covid toes' and advised supportive treatment. The triple APS antibody positivity result provided probable aetiology. Providing evidence of thrombus was problematic with false reassurance from apparently normal lower limb arterial doppler when actually popliteal arteries were not checked in view of the presence of normal flow proximally at the groin and distally in the feet. This case highlights the need to continue to search for thrombus in presence of high titres antiphospholipid antibodies and particularly in the case of triple positivity as although patient presented with colour change to toes, she was entirely asymptomatic from her PE and her left foot improved spontaneously despite a left popliteal thrombus also being present. Key learning points/Conclusion: Non-criteria manifestation of thrombocytopenia (occurs in 25% paediatric APS patients) was present throughout and patient had past history of haematuria (a recognised renal non-criteria manifestation). A paediatric specific APS criteria including these may have resulted in earlier detection of triple antiphospholipid antibody positivity and thus earlier treatment escalation and possible avoidance of thrombus. It has been reported that a high proportion of children with positive antiphospholipid antibodies don't develop a thrombus. However, it is interesting that our patient was entirely asymptomatic from her pulmonary embolus which was an incidental finding on her CT angiogram. This prompts a discussion about how much imaging should be performed in those with high levels of persistent positive antiphospholipid antibodies. Rituximab resulted in normalisation of platelet count and ESR for the first time since initial presentation. Anticardiolipin antibodies normalised, lupus anticoagulant decreased from strong to moderate and anti- B2 glycoprotein levels decreased but remained positive. Rituximab is a recognised treatment for catastrophic antiphospholipid syndrome (CAPS) but not routinely used in APS. The consistently raised ESR in an apparently clinically well patient is a reminder to continue to search for causes of inflammation. As the CRP was largely in normal range, this demonstrates the unique value of the ESR. In view of anti-B2 glycoprotein 1 antibody requiring to be verbally requested, discussions are ongoing with the laboratory department regarding the possibility of electronic request and a comment with recommendation to check other two antiphospholipid antibodies following one positive antibody result. As a result of this case, a plan will be put in place to ensure annual screening of antiphospholipid antibodies in all juvenile SLE patients in our care. It is hoped that this case report promotes discussion amongst the paediatric rheumatology community regarding further research required for development of paediatric specific APS criteria and management.
ABSTRACT
Background. COVID-19 continues to threaten public health, particularly in Native American (NA) communities, which experienced some of the highest rates of COVID-19 infection and mortality in the US. Although the risk factors and clinical characteristics of COVID-19 are well documented in the general population, there has been little research on NA patients. Methods. We present descriptive data based on chart reviews of COVID-19 patients hospitalized between April 1 and July 31, 2020 at the Whiteriver Service Unit (WRSU), an Indian Health Service site on the Fort Apache Reservation. Results. Of the 2,262 COVID-19 cases during the observation period, 490 (22%) were hospitalized and 35 (1.6%) died within 28 days. Compared to previous reports, hospitalized patients at WRSU were younger (median age 54), more likely to be female (55% female), and more likely to have comorbidities (92% at least 1, median 2). Patients under 50 (n=200) often had a history of alcohol abuse (51%) or polysubstance abuse (20%). One third of hospitalized patients (34%) were monitored at home and referred for treatment through a high-risk outreach program. Patients were admitted much earlier at WRSU than in other locations, with a median interval of 4 days from symptom onset to hospitalization compared to 7 days reported elsewhere, but over half were still transferred to higher care. Although WRSU patients had higher rates of comorbidities, the 28-day hospital mortality rate from COVID-19 was nearly half of what has been previously reported (35/490, 7% vs 15-20% reported elsewhere, p < 0.001). This trend persisted after controlling for age. Multivariate logistic regression showed that increasing age, male sex, and high BMI were significantly associated with higher risk of death from COVID-19 (overall model p < 0.001). Characteristics and outcomes of hospitalized COVID-19 patients at WRSU Conclusion. Hospitalized patients at WRSU tended to be younger but with more comorbidities than previous studies. This may reflect the fact that NAs tend to acquire comorbidities at younger ages than the general population. This may also reflect the high rates of substance abuse in younger patients, which could be an additional risk factor for severe COVID-19. We believe that the low mortality rates at WRSU are a result of our outreach program, which likely decreased the interval between symptom onset and medical treatment.
ABSTRACT
Background: In April 2020, a COVID-19 outbreak at a rural, resource-limited Department of Corrections on a Native American reservation in Arizona led to multiple epidemiologically linked cases to household contacts of recently incarcerated individuals. We describe the role of a medical recovery site for isolation of recently released inmates with active COVID-19 infection in reducing household transmission of cases tied to the correctional facility. Methods: On April 16th, an individual was contact traced to the correctional facility and was laboratory-confirmed positive, an asymptomatic index case in the jail. Testing of all inmates continued from April 16th-30th. On April 24th, decarceration began. All inmates released from facility April 24th-April 30th were contact traced for 14 days to monitor for new household cases. On April 30th, the tribe opened a medical recovery site for isolation. After opening, all individuals with active infection agreed to go to site after release. Results: Between April 24th-30th, 16 inmates were released from facility, seven were laboratory-confirmed positive. Secondary infections only occurred in households of positives. Of the seven households, four experienced secondary transmission of virus. There were 27 household contacts, six secondary infections (secondary attack rate of 30.0%). There were four hospitalizations and one death, though cause of death was not due to COVID-19 despite incidental finding. After opening of medical recovery site, all individuals with active infection (12 cases) agreed to isolation at site. This intervention resulted in no further epidemiologically linked cases from recently released incarcerated individuals to community. Conclusion: Prior to establishment of a medical recovery site on a Native American reservation, a significant burden of disease in the community was linked to recently incarcerated individuals. After opening, all actively infected individuals agreed to isolation at site, resulting in no further household transmission of COVID-19 from an actively infected recently incarcerated case. This outbreak highlights porous boundaries between correctional facilities and surrounding communities, requiring attention and resources to limit transmission of disease to protect local populations. (Figure Presented).
ABSTRACT
Background: COVID research and reporting has focused on large urban populations. However, limited data suggests that rural Native American (NA) populations are disparately impacted. We serve a well-defined NA population of ≈18,000 that is relatively geographically isolated in the White Mountains of eastern Arizona. Our first case SARS-CoV-2 was confirmed April 1st. We have since confirmed an attack rate significantly higher than most of the United States. We provide testing and case trends in addition to characteristics of the first 800 cases. Methods: We sequentially reviewed the charts of all laboratory-confirmed COVID-19 patients from April 1 to June 3, 2020. In addition to calculating prevalence and rates, we provided summary statistics that were used to describe testing breakdown, demographics, symptoms, and co-morbidities. Results: From April 1 to June 3, we tested 2,662 persons, of which 884 (33.2%) were positive. The estimated prevalence of the time of writing is 4.9% and the rate of 4,911 per 100,000 persons. Data compiled from the first 800 laboratory-confirmed patients is summarized in table 1. Median age for confirmed cases was 40.6 (IQR 28-54). 555 cases (72.1%) were symptomatic. The most common symptoms were cough (67.7%), subjective fever (39.5%), and muscle aches (36.8%). 30.6% of confirmed cases were asymptomatic at the time of testing. The majority of cases were among persons aged 30-39 years (22.9%). Some of the most common comorbidities in confirmed cases included cardiovascular disease (30.4%), substance abuse (30.1%), and diabetes (25.0%). There were 18 (2.04%) deaths. Clinical findings among symptomatic patients Conclusion: We observed a significantly higher prevalence (10-times) and attack rate of (17-times) COVID-19 in a well-defined NA population, when compared to the general Arizona population. We provide characteristics of these cases and report that nearly a third were asymptomatic at the time of testing. More research is needed to understand the rapid spread of COVID-19 in vulnerable rural communities.
ABSTRACT
Background: American Indians have an increased risk of serious complications from COVID-19 due to the high prevalence of comorbidities such as diabetes, heart disease, obesity, and asthma. To date, there has been limited analysis of COVID-19 in the AI population. This study describes the characteristics of hospitalized COVID-19 patients from a well-defined AI population in eastern Arizona. Additionally, we explored the impact of early referral via contact tracing versus those who self-presented. Methods: Retrospective chart reviews were completed for patients hospitalized for COVID from March 29 to May 16, 2020. Summary statistics were used to describe demographics, symptoms, pre-existing conditions, and hospitalization data. Results: We observed 447 laboratory-confirmed cases of COVID-19, resulting in 71 (15.9%) hospitalizations over a 7-week period and a hospitalization rate of 159 per 1,000 persons. Of the 50 hospitalizations reviewed sequentially, 56% were female, median age of 55 (IQR 44-65). Median number of days hospitalized was 4 (2-6), with 16% requiring intensive care unit support, 15% intubated, 12% readmitted, and 10% deceased. 67% had an epidemiological link, and 32% had an emergency department or outpatient clinic visit within 7 days of hospitalization. All patients were symptomatic;the most common symptoms were cough (90%), shortness of breath (78%), and subjective fever (66%). 86% of patients had a pre-existing condition;the most common pre-existing conditions were diabetes (66%), obesity (58%), and hypertension (52%, Figure 1). All patients had elevated LDH, 94% had elevated CRP, 86% had elevated d-dimer, and 40% had lymphopenia;only 10% had an elevated WBC count and 26% had thrombocytopenia (Table 1). 26% of the patients were referred in by the tracing team (Table 2). Analysis of 500 hospitalizations will be available in October 2020. Conclusion: Most AI patients hospitalized had a pre-existing condition, symptoms of cough or shortness of breath, and elevated LDH, CRP, and d-dimer. More research is needed to understand the patterns of COVID-19 related disease in vulnerable populations, like AI/AN, and to examine the utility of early referral by contact tracing teams in rural settings which may guide future tracing strategies.