The Uvea is the term for the whole eye (uvea=peeled grape). Whereas conjunctivitis looks like a red eye, it’s only really the surface that is inflamed. With uveitis, all the different tissues of the eye are inflamed. Acutely, might not look that different to conjunctivitis but painful, whereas latter usually just itchy. Anterior chamber starts to fill up with inflammatory cells so vision starts to deteriorate. An irregular pupil due to synechiae can eventually be seen, with hypopyon. Cataracts and scarring can follow.
Chronic on the other hand can be subclinical but potential for visual loss so screening important in associated conditions.
Usually idiopathic, otherwise:
Juvenile idiopathic arthritis – about 10% of patients with non-oligoarthritis, and 30% of ANA positive oligo so pretty common
HLA-B27 – with or without other B27 conditions such as Ankylosing spondylitis
Block DNA synthesis by bacteria (uniquely among antibiotics).
Good against gram negatives, including Salmonella, Shigella, Neisseria, Pseudomonas (one of the few oral antipseudomonals).
Good intracellular penetration so active against organisms such as Chlamydia, Mycoplasma, Legionella and some Mycobacteria.
Good tissue penetration including central nervous system. 80% of orally administered drug is bioavailable so the IV route is only used when absorption impaired.
But no anti-anaerobic activity, and not very good against common gram positives eg Pneumococcus, Enterococcus, Staphylococcus (in fact, use is associated with MRSA). The newer types (Gatifloxacin, Moxifloxacin, Levofloxacin) have better gram positive activity but would still not be your first line choice, and have less anti-pseudomonal activity.
Not licensed under 1yr.
Only contraindication is previous tendon problem caused by it!
Adverse Effects:
Disabling, long-lasting (even irreversible) musculoskeletal and neurological problems reported, v rarely. So only use for severe infections, unless no other antibiotic appropriate. And stop ASAP if symptoms (muscle pain, joint pain, weakness, neuropathy etc)
Seizures (+/- predisposing condition)
Tendonitis – rupture can occur within 48hrs of starting, but can also be months later! Steroids at same time may increase risk, as may renal impairment and solid organ transplants
Arthropathy in immature animals – so avoided in children (except Nalidixic acid) unless extenuating circumstances (only reversible musculoskeletal symptoms have been reported). Arthropathy occurs in CF anyway.
Can prolong QT
Photosensitivity
Valve regurgitation – so caution if preceding valve disease or other risk factor eg connective tissue disorder (Ehlers-Danlos, Marfans), hypertension (!), Turners (!)
sickle cell disease or other severe haemoglobinopathy
trisomy 21
complex or chromosomal genetic or metabolic conditions associated with significant comorbidity, multiple congenital anomalies associated with significant comorbidity
bronchopulmonary dysplasia – decisions should be made taking into account degree of prematurity at birth and chronological age
infants less than 1 year with cyanotic CHD, or haemodynamically significant acyanotic CHD with history of prematurity, or those due for corrective surgery (to avoid complications or delay)
Steroids
WHO recommends dexamethasone 150mcg/kg once daily for 10 days for severe/critical COVID19 disease, on basis of REACT metanalysis.
Severe defined as any of:
Sats <90%
Tachypnoea (>30 in over 5s, >40 over 2 etc)
Severe respiratory distress
Critical defined as ARDS, septic shock or anything else that would require critical care.
Remdesivir
For Patients at ‘high risk’ of complications (as above, in particular immunocompromise) plus:
>4 weeks of age and at least 3kg
Within 10 days of symptoms onset
NOT for patients requiring ventilatory support unless high risk, and not for ALT > 5x upper limit of normal .
5mg/kg loading dose on day 1, followed by 2.5mg/kg once a day for 4 days. May be extended to 10 days in immunocompromised.
Toculizimab is an option for pneumonitis.
Prophylaxis for high risk patients is available:
Remdesivir 3 days once daily infusions
Paxlovid (Nirmatrelvir +Ritonavir) 300/150mg BD for 5 days
Neutralising antibodies have also been tried but not in guidance.
Sotrovimab [NO LONGER AVAILABLE] – for 12-16yrs, pre-hospitalisation, PCR positive and onset of symptoms within previous 5 days. Not if new oxygen requirement or weight under 40kg. 1% vs 7% placebo hospitalisation or death (85% reduction).
Mostly against COVID spike (S) protein that facilitates host cell entry.
Pfizer vaccine is mRNA vaccine, completely in vitro derived, uses nanoparticles to aid absorption into host cells which then produce the S protein themselves from the mRNA.
AstraZeneca vaccine is chimp adenovirus vector for genetic sequence – mRNA produced once virus taken up by host cell.
From Autumn 2025, only children over 6/12 who are immunosuppressed are eligible for a COVID booster (given with flu in the autumn). The other clinical risk groups eg chronic heart/lung, DM no longer apply.
lung infections causing pneumatocoeles, which then invite aspergillomas
mucocutaneous candidiasis
eczema, eosinophilia and high IgE
PLUS bony abnormalities:
osteopenia and spontaneous bone fractures
dysmorphism: triangular jaw, wide nose, asymmetrical face
dental abnormalities eg retained primary
hyperflexibility and scoliosis
Also called Job’s (because of the Bible story, smitten by boils etc, but could equally have been CGD!) or Buckley syndrome.
Caused by STAT3 defect, part of IL6 receptor. Not actually an immunoglobulin problem! Not to be confused with Hyper IgM syndrome. But if antibiotic prophylaxis is ineffective, IVIG is sometimes used.
An autosomal recessive form without the bone abnormalities but with vasculitis esp CNS involvement described.
The virus spread beyond its original outbreak in China when a businessman became unwell on his flight out of China and died in Vietnam in 2003. Further outbreaks appeared rapidly, as far afield as Toronto. Eventually led to 8000 cases globally, but rapid surveillance and isolation measured brought the epidemic to an abrupt end within 4 months.
Super shedders exist, who have much higher infectivity (1 case on a plane infected 120 others, whereas another plane had 4 cases on board, but no secondary cases occurred!). On the other hand, there is no documented transmission by asymptomatic cases, or between children.
Incubation period is 5-7 but up to 14 days. Spread is by respiratory, fomites, and faecal-oral routes. Peak shedding occurs at peak of clinical disease hence outbreaks were often among health care workers.
Symptoms are ‘flu-like, and non-specific. Fever is universal. Those who do badly have sudden deterioration on 10th day, with ARDS. Mortality is around 10%, but very age dependent, reaching over 50% in the over 65s. Children have lower viral loads, and generally have a benign course. Compared with adults, they perhaps get more gastrointestinal symptoms than respiratory.
Children under 5 yrs are hardly affected at all – perhaps because recent coronavirus infection protective, perhaps because of reduced immune reactivity.
No long term morbidity seen in children.
The diagnosis is suggested by the paucity of clinical signs (mild crepitations only, if anything) with an abnormal chest radiograph (non-specific), and laboratory evidence of leucopenia, lymphopenia, and thrombocytopenia. Raised AST/ALT also seen.
Definitive diagnosis is by ELISA or PCR, neither of which is very sensitive, or useful early on in disease.
Interferon alpha appears to be of benefit in vitro. Otherwise supportive.
Personal Protective Equipment effective if used properly – so buddy system.
Infection control – encourage self isolation, dedicated staff etc.
Middle East respiratory syndrome, caused by a coronavirus (MERS-CoV) . See also COVID19 and SARS.
Reported 2012. More than 2000 cases so far, mostly related to Arabian peninsula, but a single case of MERS-CoV in a returning traveller led to an outbreak involving 186 cases across 16 hospitals in the Republic of Korea.
36% mortality, mostly people with co-morbidities. More than 2000 cases so far.
One of WHO blueprint priority diseases – potential for serious outbreak, no treatment or vaccine (6-7 others: SARS, Crimean-Congo HF, Ebola, Lassa etc).
Incubation time 2-5 days but up to 14. Median onset to hospitalisation 4 days.
Risk factor appears to be camel contact – milk, meat, urine.
Management
Management based on experience of SARS etc.
Infection control – negative pressure, dedicated staff, cleaning, PPE for suspected cases, self isolation for close contacts.
Hogmanay 2019, WHO were informed of cluster of cases of pneumonia of unknown cause in Wuhan city, Hubei province, China.
Novel coronavirus identified, named SARS-CoV-2. “COVID19” is associated disease. 75% genetically identical to SARS (severe acute respiratory syndrome) and 50% to MERS (Middle East respiratory syndrome) but of course these are both similarly capable of causing severe disease, whereas many coronaviruses pretty benign.
Most likely origin is from live animal markets in Wuhan, although intermediate animal (SARS was found eventually to have crossed over via civet cars). Evidence suggests that there were 2 different llineages in Wuhan, so presumably 2 different Patient Zeroes (which goes against lab leak theory).
By end of February 2020, more than 70 000 cases reported across China, 2500 fatalities. Pandemic was declared by WHO on 11th March.
Cruise ships including the Diamond Princess in Japan (over 700 cases) and the Zaandaam were particularly hard hit.
Lockdown declared in UK on 23rd March 2020.
5 variants of concern, most recently Omicron.
Risk factors
Spike (s) protein binds to ACE2 receptors, primary role of which is to convert AntiThrombin-II into AT-1,7, controlling heart rate, hypertension, vasoconstriction, sodium retention, oxidative stress, inflammation, and fibrosis, as well as enhancing baroreceptor sensitivity. ACE2 variability across populations potentially explaining particular susceptibility among people with hypertension and Africans (nearly double rate of whites) and Asians (although Indian rates lower than Bangladeshi/Pakistani). Rates among Chinese females actually lower than among Whites! [UK data]
At least 3% of severely affected people have known or previously unrecognised genetic defects in type 1 interferon production (especially TLR3 and IRF7 which amplify production).
Risk of “critical illness “ from COVID-19 RR 1.44 if overweight, 1.97 if obese. UK OpenSAFELY analysis. Death 1.27 if BMI 30-39, 2.27 if BMI>40. ACE-2 higher in obese. Plus different immune responses and challenges to ventilate.
London has double the age standardised mortality of any other part of the UK (Birmingham next), as high as 144 per 100 000 in Newham. Glasgow’s rate is about 80 [UK data].
Diabetes, cancer and poorly controlled asthma associated with death in primary care records study. Residential care homes, health care workers, social deprivation, Black/Asian groups also seem to be particularly at risk of death.
Bronx worse hit than Manhattan, despite similar population density. Higher attack and death rates among Afro-Americans. Role for air pollution too?
Pregnancy increases risk slightly, not much risk to baby although elective preterm delivery may be part of management of sick mother.
Acute neurological presentations in adults, including stroke and Guillain Barre syndrome. Thrombosis risk.
Transmission from asymptomatic cases seems to be less important than symptomatic and pre-symptomatic (1-2 days).
In adults, low lymphocytes, high neutrophils and D-dimer predict mortality.
Probably more severe than SARS but still children tend to be less severely affected than adults. Cross protection from immunity from other coronaviruses? Differences in ACE2? Some asymptomatic.
16% of hospitalised children admitted to critical care. Age under 1 yr, or age 10-14 yrs, co-morbidities, black ethnicity are risk factors for critical care admission. Mortality rate less than 1% in hospitalised [Swann, ISARIC study]. 3 PIMS deaths in England, all 10-14yrs. 70% of all COVID related deaths in non-white groups. 24% of deaths had no co-morbidities, 60% had life limiting condition. No deaths in kids with asthma, diabetes, Trisomy 21.
Wheeze uncommon.
X-ray more often negative; CT more sensitive.
Can present with GI symptoms.
One baby born to an infected mother developed severe complications.
Neutrophil and LDH counts go up, lymphocytes go down.
A small series of children with COVID-19 has shown a greater prevalence of peripheral halo (halo-sign) lung consolidations on CT.
The criteria for the definition of Acute Respiratory Distress Syndrome (ARDS) and septic shock, the guidelines for the management of sepsis and septic shock and the use of non-invasive ventilation in children are different from those of adults.
Children desaturate more easily during intubation; therefore, it is important to pre-oxygenate with 100% O2 with a mask with a reservoir before intubating.
A rectal swab may be useful in children to determine the timing of the termination of quarantine.
[Chengdu and Italian experience, from PIPSQC]
WHO supports use of dexamethasone in patients with acute respiratory presentation and hypoxia (sats<90%), tachypnoea, or severe respiratory distress. RECOVERY trial continues to study dexamethasone in neonates, plus roles for azithromycin and toculizimab.
Sotrovimab is first line treatment, Remdesivir second line is licensed in hospitalised patients in oxygen, over 12 years and over 40kg and can be considered in this age group for patients with high-risk comorbidity for non-hospitalised patients also. Treatment should be commenced within 5 days of symptom onset (Sotrovimab), within 7 days of symptom onset (remdesivir). Paxlovid (Nirmatrelvir plus Ritonavir) is alternative first line option in adults.
Paediatric multi inflammatory syndrome associated with COVID19 (PIMS-TS)
Disseminated BCG reported, implies SCID or similar major immunodeficiency.
Severe BCG reaction can also indicate underlying TB infection!
More common issues are BCG abscess, and lymphadenitis.
Abscess at injection site appears after a few weeks, can persist for months. Treatment with isoniazid has been offered but no evidence of benefit. Incision probably makes things worse!
Non-suppurative lymphadenitis (not tender, no systemic symptoms) improves over a period of few weeks. Can progress to abscess however, with eventual spontaneous discharge and sinus formation. Healing then takes several months. Drug treatment does not appear to prevent abscess formation or speed up healing.
If an axillary abscess develops, needle aspiration can prevent perforation and sinus formation. Surgical excision might be needed if matted or multiloculated.
