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Abstract
Hereditary haemorrhagic telangiectasia (HHT) leads to arteriovenous malformations (AVM) that increase the risk of haemorrhage and cause right-left shunting bypassing the reticuloendothelial system increasing the risk for recurrent infections. A 60+ year old male patient with HHT type 1 (status post six pulmonary AVM coiled embolisations) with epistaxis presented with intractable back pain, methicillin-sensitive Staphylococcus aureus (MSSA) bacteraemia and spinal MRI revealing spondylodiskitis and L4-L5 epidural phlegmon. He has an extensive history of deep-seated infections including two prior spinal infections, two joint infections and one muscular abscess—all with MSSA. The patient was treated with 6 weeks of intravenous nafcillin with symptom resolution. Infectious disease prescribed cefalexin 500 mg daily for suppression of infection recurrence considering his extensive deep-seated infection history and multiple risk factors. This case raises important questions about preventative antimicrobial management of high-risk patients with HHT, which is a grey area in current international HHT guidelines.
- Infections
- Bone and joint infections
- Arteries
- Cardiovascular system
- Back pain
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Background
Hereditary haemorrhagic telangiectasia (HHT), also known as Osler-Webber-Rendu syndrome, is an autosomal dominant bleeding disorder with high penetrance and variable expressivity that leads to the formation of arteriovenous malformations (AVMs) and telangiectasias, occurring most often in the gastrointestinal tract, brain and lung.1 2 The most common presenting symptom is epistaxis, while more severe manifestations include thrombosis, haemorrhagic strokes and paradoxical emboli, pulmonary haemorrhage, anaemia and the development of high-output heart failure.3 Clinical diagnosis of definite HHT requires three or four of the following Curacao criteria: recurrent spontaneous epistaxis, mucocutaneous telangiectasia, AVMs and positive family history.3 If two out of four criteria are met, this defines possible HHT. A study by Ferry et al showed the prevalence of HHT has increased from 6.05 to 12.12 per 100 000 people from 2013 to 2017.4 The greatest increases of prevalence occurred in the Southern USA with patients 60–69 years of age, which matches the demographics of our case.4 The authors describe study limitations that could have resulted in under-representation of patients younger than 18 or older than 65. Indeed, a study by Chowdhury et al found higher prevalence rates in North America (health jurisdiction of Alberta) of 1:3800 using provisional health administrative data.5
Pulmonary AVMs (PAVMs) are fragile thin-walled high flow low resistance circuits that lead to right to left shunting bypassing the pulmonary capillary functions of gas exchange and filtration of systemic venous blood. Consequentially, this bypass leads to changes in cardiorespiratory vascular physiology and eventual physiological compensation. The right-to-left shunt reduces PaO2, SaO2 and CaO2, typically leading to increased rest and exercise cardiac output (typically via increased stroke volume), orthostatic tachycardia, increased ventilatory drive (VE/VCO2 slope), secondary erythropoiesis and reduced exercise tolerance.6 Clinically, these can manifest as dyspnoea, cyanosis, clubbing, altered ventilatory patterns, palpitations and eventual cardiac failure. Typically, these alterations in cardiac output, haemoglobin, minute ventilation and gas patterns normalise after embolisation therapy.6 Without therapy, PAVMs rarely regress and instead tend to grow over time.
The enhanced compensatory ventilatory drive tends to overshoot, resulting in overall lower end tidal PaCO2 and venous bicarbonate then would be expected. However, patients with concomitant obstructive airway disease (asthma, Chronic Obstructive Pulmonary Disease, etc) are less able to compensate for PAVMs, thought to be due in part to impaired ability to achieve the supranormal ventilation necessary for CO2 clearance.7
The amount of blood shunted through PAVM can vary widely depending on size and number of PAVMs. The total shunt fraction (as a percentage of cardiac output) correlates negatively with resting SaO2.8 In one study, the highest percentage of shunted cardiac output was 48.8% with SaO2 of 59%. However, the majority of data points (total n=309) in this study reflected a shunted percentage of cardiac output below 10% with SaO2 between 90 and 100.
PAVMs allow for paradoxical embolisation of septic material, leading to systemic seeding and abscess formation.9 Larger total right to left shunting (reflected by lower oxygen saturations) and iron deficiency have been associated with greater risk of thromboembolic stroke, the former via enhanced platelet aggregation reversible with iron supplementation.8 It would stand to reason that larger total right to left shunting (whether from larger or multiple PAVMs) would also lead to greater risk of bacterial seeding or septic emboli; however, there are no reported data on this specifically. This is pertinent since in one study, 35% (n=16/46) of patients with HHT had a cause of death due to sepsis.9
HHT is most commonly due to mutations in genes coding endoglin (HHT type 1) or the TGF-β1 receptor component ALK1 (HHT type 2) (figure 1). The interactions of endoglin, activated by BMP9, with ALK1 and TGF-β2 initiate a Smad signalling cascade leading to genetic upregulation of processes that regulate vascular proliferation and migration, inhibiting apoptosis and coordination of response to vascular endothelial growth factor (VEGF).3 10 11 Disturbance of this pathway due to the mutations of HHT has consequences including increased endothelial hyperplasia, inflammation, increased and uncontrolled VEGF signalling and angiogenesis, imbalance in angiostatic TSP-1 expression (in HHT type 1) and imbalance of vascular destabilisation factor Ang-2 (in HHT type 2), altogether predisposing to the formation of fragile mucosal telangiectasias that easily break and bleed, as well as the formation of AVMs.12
Molecular mechanisms of arteriovenous malformation (AVM) and increased infection susceptibility in hereditary haemorrhagic telangiectasia (HTT) type 1. eNOS (endothelial nitric oxide synthase); VEGF (vascular endothelial growth factor). Illustration created using BioRender.com.
Endoglin is also important for vascular function through its activation of endothelial nitric oxide synthase, the absence of which in HHT leads to oxidative stress with reduced myogenic tone and increased dependence on superoxide for mediation of physiological vascular dilatory response.13 This aspect of HHT can be managed through the therapeutic use of N-acetyl cysteine.13 14
Endoglin activation also leads to activation of zyxin and ZRP-1 for maintenance of actin cytoskeleton organisation.10 The extracellular RGD (arginine–glycine–aspartic acid) region of endoglin receptor interacts with platelets, leucocytes and mural cells.10 Through this interaction, endoglin contributes to platelet stabilisation, mural cell recruitment for maintenance of vascular maturity and permeability, and regulation of leucocyte adherence and transmigration.10 15
The molecular, cellular and mechanical consequences of HHT lead to increased risk of infection in these patients.16 17 Recurrent epistaxis leads to a pathway, especially for skin flora such as Staphylococcus species, to enter the bloodstream. Pulmonary AVMs lead to shunting and mechanical bypass of the lung’s macrophage filtration in the reticuloendothelial system, reducing clearance of systemic bacteria.18 Once infection has occurred, the dysregulation of leucocyte adherence and migration leads to disrupted ability for proper immune cell response. Furthermore, endoglin involved in monocyte differentiation and expression of NAPH oxidase 2 and myeloperoxidase and mice lacking the endoglin gene are more susceptible to infection with reduced phagocytotic capacity and reduced TNF-a, IL-1β and IL-6.16 19–21 T-helper cells in HHT exhibit dysregulation of CXCL12/CXCR4 chemotaxis in patients with a history of severe infections, and T cell populations are reduced in patients with HHT and anaemia.22–24 Patients with HHT often exhibit iron-deficiency anaemia, increasing infection risk and transfusion-related transient iron overload can also increase risk for cerebral abscess.25 26 Finally, AVMs and arterial aneurysms can occur in the spleen theoretically leading to bypass of splenic filtration function or necessitate splenectomy, leading to increased risk of infection from encapsulated organisms,16 27–30 although this is not a commonly seen occurrence in clinical practice.31
In a study by Dupuis-Girod et al, it was outlined that cerebral abscess was the most common infectious consequence of HHT, followed by septicaemia, septic arthritis/osteomyelitis/erysipelas, muscle abscess, spondylodiscitis, hepatic abscess, and less predominantly endocarditis, pneumonia, pyelonephritis, appendicitis and peritonitis.32 The most common agent in this study causing extracerebral infections was Staphylococcus aureus, accounting for 14 out of 45 (31.1%) cases. Management of infectious risk starts with controlling the sources and entrance vectors. This can be achieved through VEGF inhibitors such as bevacizumab or other anti-angiogenic agents such as thalidomide.12 33 34 Thalidomide also stabilises the vasculature through recruitment of pericytes as well as encouraging vessel maturation.35 36 Tranexamic acid is used to reduce epistaxis. AVMs can be clipped, embolised or surgically ligated, with telangiectasias being treated with laser therapy or sclerosing agents.
Despite these measures, rates of infection in HHT remain high. Rates of infections leading to hospitalisation include 13.6–28.6% of patients with HHT.16 Brain abscess rates in particular are 5–9%, which is 1000 times higher than the general population.37 There is currently no clear consensus on how to properly manage infection risk in patients with HHT and recurrent high-risk deep-seated infections. We present a case of a man with type 1 HHT with a history of at least six deep-seated infections who represents such a dilemma.
Case presentation
The patient is a 60+ year old Caucasian male with HHT type 1 with medical history of six coiled pulmonary AVMs (two right, four left), polymyalgia rheumatica and a history of multiple septic joints (L3-4 1985, T12 1991, right knee 2017, left ankle 2018, splenius capitis abscess 2022) who presented with acute, worsening left-sided mid back pain for 1 day (table 1). Pain radiated to the upper abdomen and epigastric region with subsequent distention and a sensation of ‘tightness’ under ribcage. He ranked the pain as 5/10 at rest (10/10 with exertion) and in his words said it was at ‘the T12 level’. The patient had tried ibuprofen 800 mg and extra strength acetaminophen with no improvement. He denied injury or falls and had no change in exercise routine. He endorses having a recent ‘chest cold’ the week prior for which he had a lingering cough on top of chronic dyspnoea. Review of systems pertinent positives includes pain worse with spinal flexion and extension, dyspnoea and cough, and epistaxis, while pertinent negatives include no nausea or vomiting, no loss of bowel or bladder function, no wheezing or crackles, no extremity loss of sensation, paresthesia or weakness. Vital signs on admission included a temperature of 98.3°F, blood pressure of 141/94, heart rate of 99, respiratory rate of 16, SpO2 of 96% and body mass index of 36.7. Physical examination revealed left paraspinal lumbar tenderness, hypertonicity near T12, normal range of motion, 5/5 extremity strength, diffuse upper abdominal tenderness without rebound or guarding, normal bowel sounds and negative Murphy’s sign. Hospital course summary and timeline of events are summarised in figure 2A,B.
Illustration of recurrent infections and hospital complications (A) and clinical course timeline (B). Illustration created using BioRender.com. AVM (arteriovenous malformation); CTPE (computed tomography with pulmonary angiogram protocol); MSSA (methicillin-sensitive Staphylococcus aureus); PE (pulmonary embolism); PICC (peripherally inserted central catheter).
Patient history
Prior to our (the internal medicine service) evaluation of the patient, the emergency department workup included a chest, abdomen, pelvis CT scan revealing spinal degenerative disease and known chronic pneumobilia but no acute abnormality. Pertinent laboratory findings included leucocytosis (12.7 with 79% neutrophils), an erythrocyte sedimentation rate of 48 and C-reactive protein level of 40.
MRI obtained on hospital day 2 showed diskitis with spinal epidural phlegmon of L4-L5 (figure 3). Neurosurgery was consulted and recommended medical management, as no drainage could be performed on the phlegmon. The patient was initiated on empiric vancomycin and piperacillin-tazobactam. Otolaryngology was also consulted on day 2 for significant epistaxis management, and their recommendations included tranexamic acid-soaked nasal tampon, four times daily nasal mist spray, 5 sprays of nasal oxymetazoline during bleeding events and two times per day nasal petroleum jelly. On hospital day 3, the patient had increased back pain and met SIRS criteria with fever (Tmax 103°F), tachycardia (108) and elevated white blood cell count (13.1). Subsequently, 3 out of 3 blood cultures (drawn on admission) were positive for S. aureus. The antibiotic regimen was switched to nafcillin following resulting sensitivities (showing methicillin sensitive). Immunoglobulin levels (IgG, IgM, IgA) were also obtained and were within the normal range, likely excluding a primary immunodeficiency such as common variable immunodeficiency sometimes seen concomitantly in patients with HHT.
T1-weighted MRI with contrast images of spinal epidural phlegmon on hospital day 2 (A), 4 (B) and 6 (C). Day 2: Prominent predominantly anterior epidural enhancement diffusely throughout lumbar spine and to a lesser extent the lower thoracic spine on the right side. No peripherally enhancing with central low-density collection to suggest epidural abscess. Fusion of T12-L1 and partial fusion of L4-L5 could represent remote spondylodiskitis. Days 4–6: Resolution of epidural phlegmon.
Repeat MRI on hospital day 6 revealed resolving phlegmon. Since the patient had a bloodstream infection with an endocarditis causing bacteria with one major and one minor Dukes criteria, echocardiographic endocarditis screening was performed. Transthoracic echocardiography revealed minor tricuspid, mitral and aortic regurgitation. Transoesophageal echocardiography did not elucidate any valvular vegetations ruling out endocarditis, although the aortic valve did exhibit Lambl’s excrescence, with significant patent foramen ovale (PFO, >25 bubbles right to left shunt at rest) and ejection fraction of 55%.
Hospital course was further complicated by hyponatraemia, thrombocytopenia, pneumonia versus viral upper respiratory infection and ileus, all resolved by discharge (figure 2A). Specifically, on hospital day 4, platelets were low at 89 000 without visible purpura and haematology was consulted. Laboratory findings included normal prothrombin time, partial thromboplastin time, high fibrinogen (707) and D-dimer (1.67). The patient was HIT antibody negative with an International Society on Thrombosis and Haemostatis (ISTH) score of 4, ruling out heparin-induced thrombocytopenia or disseminated intravascular coagulation. On hospital day 5, the patient became dyspnoeic requiring oxygen and Computed tomography with pulmonary angiogram protocol ruled out pulmonary embolism but did show new bilateral pulmonary oedema. The patient exhibited pre-renal acute kidney injury (FeNa 0.4%) with hyponatraemia to 127 that responded to normal saline bolus. Ileus responded (per X-ray) after aggressive bowel regimen with docusate/senna, SMOG enema, polyethylene glycol and bisacodyl suppository by day 7, which relieved the radiating abdominal component of his back pain.
By day 11, the patient’s repeat blood culture had no growth for 5 days. Prior to the hospitalisation, a blood culture did not show growth until the fifth day, so all cultures were monitored for 5 days prior to confirming negative for growth. The patient was discharged on hospital day 13 in stable condition with peripherally inserted central catheter for an additional 6-week nafcillin treatment course. Cefalexin 500 mg daily was started as outpatient for prolonged bacterial suppression after nafcillin treatment was completed.
Outcome and follow-up
Outpatient, the infectious disease team made the decision to put the patient on prophylactic cefalexin 500 mg daily for bacterial suppression. X-ray of the spine 6 weeks after discharge did not show obvious recurrent pathology despite some recurrent 3/10 pain, worse with exertion. Degenerative changes and fusion at T12-L1 were similar to previous MRI images. Seven weeks post-discharge, the patient had an MRI of his right knee for pain which only revealed arthritic changes and was not consistent with septic arthritis. His polymyalgia rheumatica has also since resolved and has been off steroids since 3 months post-discharge. His back pain eventually resolved by 6 months post-discharge, and the patient cancelled his neurosurgery follow-up appointment.
At a primary care appointment 6 months post-discharge, he has had some worsening dyspnoea with exertion above his baseline dyspnea. Importantly, outpatient CT scanning diagnosed at least one new medial right lung AVM measuring 6–7 mm along with several enlarging pulmonary nodules (his last screening CT scan was in 2015). Pulmonary referral was subsequently scheduled but has not yet been completed. At another primary care appointment, the patient was evaluated for coeliac disease at his request (due to family history), but testing was found to be negative, with IgA levels mildly elevated.
A subsequent CT coronary angiography revealed CAD-RADS 4A with subsequent invasive angiography planned. The patient has had no infection recurrence during a 9-month follow-up appointment with the infectious disease team—he is agreeable to continue suppressive cephalexin 500 mg once daily with a plan for next follow-up in 1 year, which will be 21 months after hospitalisation.
Discussion
Strategies for preventing infections in HHT has been an evolving topic over the last 5 years. There have been several proposed approaches including (1) expanded vaccinations, (2) limited antibiotic prophylaxis in the context of dental or surgical procedures, and/or (3) lifelong antibiotic prophylaxis.
The vaccine expansion strategy, suggested by Rodríguez-García et al, is akin to the approach for splenectomy patients covering Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis (as well as vaccines for influenza, herpes zoster and hepatitis B).16 However, in response to this strategy, Al-Samkari et al explained that from 1984 to 2017, over six retrospective studies and a case series, there had not been any reported cases of infection by these encapsulated agents but rather the most common causes of infection were skin or oral anaerobic species such as Actinomyces, Fusobacterium, Peptostreptococcus, aerobic Streptococcus, or pertinent to our case from S. aureus, which is associated with colonisation in the nares and translocation during epistaxis.31 S. aureus represented approximately 7.5–8.5% of the infections from these studies.31 The authors conclude that the evidence for this vaccination strategy is not strong enough for consideration in the general HHT population.
In a 2018 HHT management review, Kritharis et al instead reinforced that antimicrobial measures should include prophylaxis prior to dental or surgical procedures with penicillin (clindamycin if penicillin allergic) and suggested the use of intravenous with filters.38 The European Reference Network on Rare Multisystemic Vascular Diseases (VASCERN, formed in 2017) explored this topic in their 2017 HHT workshop (published in 2018) as one of five HHT outcome measures of interest.39 40 Unanswered questions from that session included prophylactic antibiotics in the settings of interventions for all patients with HHT, or just with pulmonary AVMs (typically in HHT type 1) and the utility of long-term penicillin prophylaxis for high-risk patients.39 40 The 2020 International Guidelines and 2022 VASCERN largely reiterated these sentiments with emphasis on antibiotic prophylactic strategy for pulmonary AVMs as one time for invasive procedures without mention of when longer term antibiotic prophylaxis is appropriate.41 42 These strategies do not encompass higher risk patients including those with recurrent deep-seated infections and histories of infections in high-risk areas, such as our patient with three spinal infections with S. aureus.
The presented case represents a high-risk patient with at least six hospitalisations due to recurrent infections with the same microbial agent (S. aureus) in high-risk locations including the joints and spine. He did not have any recent dental care nor any recent invasive procedures for which the one-time prophylactic antibiotic strategy would have been appropriate. Presumed source of bacteria was bacterial translocation from epistaxis, as no other source identified, although it is possible that there was seeding from a chronic unidentified source such as a chronic spinal osteomyelitis. Our patient had other risk factors for infection. He had been on low-dose oral glucocorticoids for treatment of polymyalgia rheumatica for 21 months. Glucocorticoids for polymyalgia rheumatica have been associated with a dose-response dependent increase in risk for infections with a cumulative risk of bacterial infection of 3.4 (CI 3.0 to 3.8) for doses 0–4.9 mg relevant to our patient.43 Our patient also has a PFO, which further increases his risk for deep-seated infections in general and has been a topic debated by VASCERN whether this is significant for HHT.39 44 Other components of HHT that increase infectious risk include iron deficiency, iron infusion and red cell transfusion. His lowest haemoglobin was 132 g/L (mild anaemia) and did not require transfusions in the preceding 6 months or in the 9 months since discharge. Bevacizumab itself, while not immunosuppressive, also has been associated with minor increases in infectious risk, although it minimises epistaxis and reduces AVM formation which would be protective.45 46
Due to the history of recurrent high-risk infections, the infectious disease team made the outpatient decision for lifelong cefalexin 500 mg daily. Daily antibiotic suppression for this patient is warranted due to repeated deep-seated infection, high-risk location of infection (spine), and to limit subsequent hospitalisations and risk of acquiring colonisation with hospital-acquired MRSA colonisation. Lowering infection risk is also important in this patient because his pulmonary AVMs and PFO led to him having a higher risk for cerebral abscess, which have high morbidity and mortality.47 His PFO is also significant because it would interfere with diagnostic studies (via transthoracic contrast echocardiography) of any possible physiologically significant micro-PAVMs not otherwise detectible by CT.6
The prolonged-lifelong antibiotic strategy is not undergone lightly, as the practitioner must balance antibiotic stewardship versus patient well-being in these cases. This decision is made without clear guidelines. Important questions for consideration are these; what should the exact threshold be to advance a patient with HHT from the recommendation of antibiotics prior to risky procedures only to the recommendation of prolonged-lifelong antibiotic prophylaxis? How many hospitalisations are required? Would just one high-risk infection (cerebral abscess, spinal) be enough to warrant this strategy? Should the severity of infection or virulence of the species (such as MRSA) factor into this decision-making? If a patient does not warrant lifelong antibiotics, is there any merit for consideration of prophylactic antibiotics or nasal decolonisation after significant epistaxis events requiring nasal packing?48–50 Should other bodily skin sites common for MRSA be surveyed and decontaminated with strategies such as antiseptic chlorhexidine body washes?51 Should stool be surveyed for MRSA or other common pathogens due to the possibility of systemic spread through gastrointestinal AVMs in specific subsets of patients with HHT?52 53
Due to provider training emphasising antibiotic stewardship, this decision may cause cognitive dissonance that biases providers towards withholding antibiotics, even in situations where it may be appropriate. Indeed, even for the single-dose antibiotic prophylaxis strategy for dental/interventional procedures, it was found that only 8% of patients referred for HHT for pulmonary AVM embolisation at one UK centre had received this advice.40 Lack of general practitioner education on HHT was also cited as a contributing factor for the lack of antibiotic prophylaxis. This prompted clearer guidelines and emphasis from VASCERN that 100% of patients with pulmonary AVMs should have written advice on prophylactic antibiotic use prior to dental or surgical procedures.40 Similar attention should be made for cases of recurrent high-risk infections. We appreciate this may be a difficult task, as such cases are certainly rarer, especially in the literature, where reported cases of HHT infections often focus on one single infection event. However, we did identify 13 cases of recurrent, multiple or high-risk cases of S. aureus in HHT, of which the prolonged-lifelong antibiotic strategy was used in three cases (table 2). The greatest number of repeat infections in any one patient was five (our patient had six infections).
Review of recurrent, multiple or high-risk Staphylococcus aureus infections in HHT and reported treatments
Importantly, our patient’s clinical situation is unique in several ways compared with the majority of patients with HHT, and therefore, we want to emphasise that we are not suggesting more liberal usage of antibiotics in general for patients with HHT. For example, in one study of 136 patients with HHT undergoing PAVM embolisation, only 17.6% had greater than four PAVMs.54 Our patient’s numerous PAVMs (a total of seven with at least one currently not embolised), PFO (another significant right to left shunt and it excludes the ability to diagnose microscopic PAVMs) and extensive history of repeat and high-risk infections likely put him at greater risk than the general HHT population.
One protective factor for our patient is that he has appropriate immunoglobulin levels (with mildly elevated IgA) indicating no concomitant primary immunodeficiency sometimes seen in HHT or patients with PAVMs.55–57 According to Guilhem et al, IgA and IgG tend to be elevated, while IgM, CD4, CD8 and CD26 T cells, and natural killer cells tend to be lower in patients with HHT.22 58 Lower IgM was significantly associated with severe infection history in patients with HHT.58 There appears to be no significant difference in innate immunity of patients with HHT.58 Endoglin and ALK1 are heavily expressed in lymphocytes relating to their role in CXCR4-SDF-1 chemotaxis which is disrupted in HHT.22 Average percent lymphocytes throughout our patient’s hospitalisation were 9.46% (range 3.2–19.6%; normal ~20–50%), and average absolute lymphocyte count was slightly reduced at 0.725×103/µL (range 0.2–1.1; normal range=0.8–3.2). Lymphocytes were not stratified for T cell subtypes. He exhibited normal levels of basophils, eosinophils and monocytes, and normal to elevated neutrophil counts. Overall, it appears that our patient’s epistaxis and sources of right to left shunting are a greater contributory risk factor for infection reoccurrence than primary immune dysregulation other than theoretically altered chemotaxis.
HHT is a disorder of dysregulated angiogenesis that leads to the formation of AVMs with classic risks of bleeding. Infections are common in this population due to dysfunctional immune migration and response, right to left pulmonary shunting and increased bacterial translocation from epistatic nasal telangiectasias. Much of the focus in the field has been on preventing infection in the general HHT population with one-time prophylactic antibiotics after dental/surgical interventions. However, this does not encompass patients that are at high risk for infections or that have a history of recurrent infections. Long-term tracking and reporting of HHT patient lifetime infection events, stratified for HHT subtypes, is important to further guide best management practices with regard to antimicrobial strategy.
Learning points
Hereditary haemorrhagic telangiectasia (HHT) leads to a propensity towards infections, especially in type 1 HHT. Factors that increase the risk of infection include pulmonary AVMs, patent foramen ovale, reduced immune cell migration and function.
Patients with HHT commonly suffer from relentless epistaxis, which is often an entry point for Staphylococcus aureus.
Patients with HHT should at least receive one-time antibiotic prophylaxis when receiving dental/surgical interventions.
For patients with recurrent, multiple and/or high-risk infections, lifelong antibiotic suppressive therapy may be warranted.
More data from longitudinal tracking of patients with HHT for recurrent infection trends would further shed light on appropriate thresholds to initiate lifelong antibiotic prophylaxis.
Ethics statements
Patient consent for publication
References
Footnotes
Contributors The following authors were responsible for drafting of the text, sourcing and editing of clinical images, investigation results, drawing original diagrams and algorithms, and critical revision for important intellectual content: EPT, IA, JC, JB. The following authors gave final approval of the manuscript: EPT, IA, JC, JB.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.