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Mycoplasma pneumonia

Infectious disease, Respiratory

Most common bacterial cause of pneumonia in children requiring hospitalisation (Clin Infect Dis 2019) – relatively older children (5+ yrs), more likely to have had recent antibiotics but otherwise clinically indistinguishable.

Studies have indicated that the prevalence of M. pneumoniae in the upper respiratory tract (PCR) is similar among asymptomatic, healthy children and children with a symptomatic respiratory tract infection!  Current diagnostic procedures for M. pneumoniae are unable to differentiate between bacterial carriage and infection!

Note rapid worldwide emergence of macrolide-resistant (MRMP) isolates.

Meyer Sauteur PM; van Rossum AM; Vink C.  Current Opinion in Infectious Diseases. 27(3):220-7, 2014 Jun. PMID UI: 24751894

Macrolide allergy

Allergy

The majority of cases reported are non immediate reactions eg maculopapular rash, urticaria. The incidence of anaphylactic reactions is extremely low.

Less than 15% of those suspected of having macrolide allergy are finally confirmed as allergic, mainly by direct provocation testing.

Cross-reactivity between the different macrolides is variable and little information is available.

Current Opinion in Allergy and Clinical Immunology 14(4), August 2014, p 278–285. DOI: 10.1097/ACI.0000000000000069

Penicillin allergy

Allergy

Children with pneumonia with a label of penicillin allergy were found to have:

  • higher risk of hospitalization (RR 1.15)
  • acute respiratory failure (RR 1.27)
  • and need for intensive care (RR 1.46; 95% CI, 1.15-1.84)
  • increased cutaneous drug reactions (RR 2.43)

[US Journal of Allergy & Clinical Immunology in Practice.  11(6):1899-1906.e2, 2023 Jun.]

Cephalosporins

Atanaskovic-Markovic et al found that cross-reactivity between cephalosporins and penicillins varied between 0.3 and 23.9%, being higher among penicillins and between first-generation and second-generation cephalosporins.

However, it has recently been shown that all penicillin allergic children can tolerate cefuroxime, presumably as it has a different side chain.

Cross-reactivity appears to be higher in immediate reactions, and when penicillins and cephalosporins are identical or similar in the R1 side chain, as happens with the first and second-generation cephalosporins.

Currently BNFc says to avoid cefalosporins if history of immediate penicillin hypersensitivity, but if use of cefalosporin is “essential” then can be used (but not cefalexin!).

Canadian study did oral challenges for non-blistering rashes – safe – but mostly cefprozil allergy (and linked to food allergies).

De-labelling

In hypothetical case of de-labelled patient, 47% of anaesthetists would not prescribe penicillin to patient anyway (n=5000)!

Primary care don’t always remove label even after de-labelling! (patient held records would help…)

Needs culture change in primary care and paeds of documenting reactions!

Make sure note is added to patient record when de-labelled. Electronic labels don’t necessarily help – not always possible to remove an allergy label from drug prescription system, depending on the system, may only allow subsequent note to be added.  Free text systems do not encourage accurate description!

Alabama trial from NIHR to report on RCT of de-labelling in primary care; SPACE study in secondary care (nurse/pharmacist delivered).

See Testing for antibiotic allergy.

Lyme Disease

Cardiology, General paediatrics, Infectious disease, Microbiology, Neurology, Rheumatology

Borrelia (spirochaete) infection, spread by ticks (Ixodes), common in localized areas of Europe and North America (forest environments).

Differential includes possible co-infection from other tick born organisms viz anaplasmosis, or babesiosis.

Vaccine available if likely to be at risk.

Clinical

Infection occurs a minimum of 48 hours after bite!

Skin – Erythema migrans is the classic skin lesion, a spreading ring usually at the site of the bite but can be multiple and at different sites.  Typically not hot, itchy or painful. Takes a while for central clearing to develop. Develops over 1-4 weeks (from 3 days to 3 months!), can last months.  Looks like erythema multiforme, but time scale different.  Insect bite hypersensitivity/superinfection looks similar but usually hot, itchy and/or painful, and develops/recedes within 48 hours!

Lyme lymphocytoma is a painless bluish red nodule or plaque, especially on the ear but also reported on the nipple and scrotum.  More common in children.  May persist for months, can precede other features.  Acrodermatitis chronica atrophicans (ACA) is almost exclusively seen in adults, predominantly women, and is an eruption with chronic, progressive red or bluish-red lesions, usually on the extensor surfaces, with later atrophic, fibroid or sclerodermic changes.

Consider Lyme as possible (but unlikely) cause for:

  • fever and sweats
  • swollen glands
  • malaise
  • fatigue
  • neck pain or stiffness
  • migratory joint or muscle aches and pain
  • cognitive impairment, such as memory problems and difficulty concentrating (sometimes described as ‘brain fog’)
  • headache
  • paraesthesia

Arthritis – uncommon, presents as recurrent inflammation of 1 or more large joints, usually the knee. Swelling can be disproportionate to pain.  Can become more persistent – in a minority, despite treatment, inflammation becomes chronic (presumably immune-mediated).

Carditis occurs rarely, and almost always with other clinical features.  Usually partial heart block, but can be complete, usually resolves within a week.

Neurological – isolated facial palsy, meningitis, other cranial nerve palsies, meningoencophalitis, polyradiculopathy.  There is a small proportion of children who can present with non-specific headache, fatigue, neck pain without clear neurological signs (and also the rare case of raised intracranial pressure).

Other rare disease manifestations include uveitis, iridocyclitis and keratitis.

Diagnosis

For erythema migrans, clinical diagnosis is adequate, and antibodies only positive in 30-70% anyway!

Use a combination of clinical presentation and laboratory testing to guide diagnosis and treatment in people without erythema migrans. Do not rule out diagnosis if tests are negative but there is high clinical suspicion of Lyme disease.

  • Offer an enzyme-linked immunosorbent assay (ELISA) test for Lyme disease – consider starting treatment with antibiotics while waiting for the results if there is a high clinical suspicion. (Test for both IgM and IgG antibodies)
  • If the ELISA is positive or equivocal, perform an immunoblot test for Lyme disease (again, consider starting treatment with antibiotics while waiting for the results if there is a high clinical suspicion). [Western blot increases specificity, but cut offs (for both serology and Western blot) can be an issue, with potential false positives for other acute infections and autoimmune conditions.  Definitely needs to be an approved lab…]
  • If ELISA negative and the person still has symptoms, review their history and symptoms, and think about the possibility of an alternative diagnosis.  If tested within 4 weeks from symptom onset, repeat the ELISA 4 to 6 weeks after the first test.
  • If Lyme disease is still suspected in people with a negative ELISA who have had symptoms for 12 weeks or more, perform an immunoblot test.  If negative, consider synovial fluid aspirate/biopsy, or lumbar puncture [PCR – culture is difficult – or CSF antibodies for neuroborreliosis; consider for isolated facial palsy]
  • If immunoblot negative and symptoms resolved, no treatment is required.

For early neuroborreliosis, antibodies 80% sensitive, rises to virtually 100% for late or ACA.

Early antibiotic treatment is also believed to potentially block antibody production.

Antibodies can then persist for months or even years after successful treatment of the infection, so repeat testing is not useful for monitoring treatment success.

First line ELISA test can have false positives for other spirochaetes, glandular fever and autoimmune conditions.

The idea that there are seronegative “chronic Lyme” cases has little evidence to support it, with only 2 possible cases reported (ACA and arthritis, not neuro).

NICE says “Discuss the diagnosis and management of Lyme disease in children and young people under 18 years with a specialist, unless they have a single erythema migrans lesion and no other symptoms. Choose a specialist appropriate for the child or young person’s symptoms dependent on availability, for example, a paediatrician, paediatric infectious disease specialist or a paediatric neurologist.”

Treatment [check NICE]

The most commonly recommended first-line treatments for different stages of Lyme borreliosis in Europe are:

  • Erythema migrans/borrelial lymphocytoma:  10-14 days Doxycycline if 9yr+ (initially 5 mg/kg in 2 divided doses on day 1, then 2.5 mg/kg daily in 1–2 divided doses, max dose 200mg, for a total of 21 days, option for higher dosing) – 10 days courses of doxy effective in US trials.  Else Amoxicillin 50mg/kg/d, max 500mg TDS (10-14 days)[BNFc says 30mg/kg/d, max 1g, TDS for 21 days].  Don’t delay treatment pending test results.  Scandinavia use 10 days Pen V (100mg/kg/d, max 1000mg TDS). BNFc says Azithromycin as alternative.
  • Isolated facial palsy: 14 days Oral doxycycline  – else as above.  Doesn’t probably help resolution but may prevent later complications.
  • Meningitis/radiculopathy: PO Doxycycline or IV Ceftriaxone  50-100mg/kg/d, max 2g daily (14-21 days). [BNFc talks about CNS disease separate from cranial/peripheral nerves]
  • Encephalitis, myelitis: Ceftriaxone (14 days)
  • Lyme arthritis: Doxycycline (28 days) else Amoxicllin (21-28 days)
  • Carditis: Ceftriaxone during pacing, else PO doxycycline (14 days)

Ceftriaxone is the most commonly preferred parenteral agent, with once-daily dosing facilitating outpatient treatment. Recent prospective studies have shown that oral doxycycline is noninferior to ceftriaxone in neuroborreliosis, and it is now recommended in Europe for the treatment of acute facial palsy (FP), meningitis and radiculoneuritis. Ceftriaxone currently remains the preferred choice for children with other presentations of neuroborreliosis and for those with contraindications to doxycycline.

Several recent EM treatment studies have incorporated noninfected control groups. Excellent responses were seen, with resolution of rash within 7–14 days. Nonspecific symptoms including headache, myalgia, arthralgia, fatigue and parasthesias were no more common in cases than controls at 6-month follow up.

[position statement by the British Infection Association, J Inf 2011;62:329]

[Pediatric Infectious Disease Journal Volume 33(4), April 2014, p 407–409]  

Clostridium difficile

Gastro, Infectious disease

Classically causes pseudomembranous colitis.  A soil anaerobe, spore producing.

In children, most will have had antibiotics within past 4-12 weeks, other risk factors are past and/or prolonged hospitalization.  Many comorbid conditions associated esp cancer, inflammatory bowel disease. Clindamycin was classically the antibiotic most associated but any will do.

There may be fever and abdominal pain.  Colitis can mimic (or exacerbate) IBD.  Severe infection unusual.  Markers established in adults for severe infection resulting in colectomy or transfer to ICU have not been shown to correlate in kids.

“Pseudomembranes” are a non-specific endoscopy finding.  Not always tested for automatically by lab, you may need to specify. Toxin test (not 100% sensitive).

Current Opinion in Pediatrics. 26(5):568-72, 2014 Oct. PMID 25032717

Meningococcus W

General paediatrics, Infectious disease

MenW now appears to be endemic in England, with cases now in young children, and across all regions.  Previously used to only be seen in epidemics, particularly related to Haj travel.

Numbers now about 1/4 those of MenB.

Mortality rate approx 12%.  Some adult cases of septicaemia progressing rapidly to death.  Some atypical presentations eg arthritis, severe pneumonia, GI symptoms without non-blanching rash (still rapidly progessive).

JCVI have recommended vaccinating all UK adolescents aged 14-18 years of age (school years S3-S6 in Scotland) with MenACWY as soon as practicable, this is in addition to introduction of Bexsero® vaccine (MenB) for all infants in Scotland.

Ehlers-Danlos syndrome

General paediatrics, Genetics, Orthopaedic, Rheumatology

Covers a spectrum of problems, classified by Beighton (as in hypermobility, Marfans etc). “Vast genetic heterogeneity and phenotypic variability” – 2017 proposed classification includes 13 subtypes!

Classically:

  • joint laxity (hypermobility),
  • skin hyperextensibility,
  • tissue fragility (easy bruising, skin splitting, hernias, prolapses).

Stretchy skin can feel soft and doughy.  Associated with atrophic scars (that look like bad healing).

Mild myopathy seen.

  • Type 1 is severe, commonly born prematurely due to premature rupture of membranes, joint and skin laxity are gross with frequent orthopaedic problems. History of hernia repair? Aortic root dilatation and mitral valve prolapse have been reported but evidence on prognosis is still conflicting.
  • Type 2 is milder and so often underdiagnosed.
  • Type 3 is benign joint hypermobility without skin problems!
  • Type 4 is the rare but severe form where risk of arterial rupture, mostly between ages 20-40. Autosomal dominant so may be history, sometimes characteristic facies. Abnormal bruising is characteristic and the skin is unusually translucent but paradoxically it is not especially hyperextensible, and hypermobility may not be very obvious (perhaps only in fingers)! Problems rarely present before age 20 so important to pick up. Arterial rupture can affect anywhere – aneurysm or bizarre fistula may precede, else trauma or surgery may be a trigger. Bowel rupture is often seen although not usually lethal, pregnancies can be affected by uterine rupture +/- haemorrhage.

Sheffield does genetic testing.

Coeliac disease

Gastro, General paediatrics

Autoimmune process triggered by gluten, distinct from type 1 IgE mediated wheat allergy –  leads to subtotal villous atrophy in terminal ileum. Multifactorial, genetics important – at least 90% positive for DQA1*05 and DQB1*02 alleles that code (confusingly) for DQ2 and/or the DQB1*03:02 allele that codes for DQ8 molecules.  The risk of having coeliac disease without these variants is less than 0.1% so good negative predictive value, but very little positive predictive value – you may not have it now, but you may well get it in the future.

1 in 200, mostly undiagnosed/adult, decreasing in children. More girls than boys, 10% risk to 1st degree relatives.

Randomized trial of early introduction of gluten (4 months, rather than UK recommended 6 months) in 1300 babies found not a single case of coeliac disease at age 3, cf 7 cases in later introduction group (JAMA Ped 2020) – similar result for egg/peanut allergy (same EAT study).

Signs

Become less convincing the older you are! Can present even in infancy, although diagnosis may be delayed for a year or more.

Consider in patients with:

  • Chronic or intermittent diarrhea
  • Chronic constipation not responding to usual treatment
  • Chronic abdominal pain
  • Distended abdomen
  • Recurrent nausea, recurrent vomiting

Should also be considered for these extra-intestinal symptoms:

  • Weight loss, failure-to-thrive, stunted growth/ short stature
  • Delayed puberty, amenorrhea
  • Irritability, chronic fatigue
  • Neuropathy
  • Arthritis/arthralgia
  • Chronic iron-deficiency anaemia
  • Decreased bone mineralization (osteopenia/osteoporosis), repetitive fractures
  • Recurrent aphthous stomatitis
  • Dermatitis herpetiformis–type rash
  • Dental enamel defects
  • Abnormal liver biochemistry

And consider for these specific situations:

  • First-degree relatives with CD
  • Autoimmune conditions: T1DM, thyroid disease, liver disease
  • Down syndrome, Turner syndrome
  • William’s-Beuren syndrome
  • IgA deficiency

[ESPGHAN guidelines 2020]

Diagnosis

Biopsy is no longer essential for diagnosis in children with high serum IgA class antibody concentration against transglutaminase 2 values (10 times the upper limit of normal) with appropriate tests and positive endomysial antibodies (EMA-IgA) in a second serum sample, even in absence of symptoms. Shared decision making with parents recommended.

Children with positive IgA class antibodies but under 10x ULN should have biopsy.

Beware IgA deficiency (associated with coeliac disease, which gives false negatives for IgA TTG – our lab can see this when they do the test, so no need to request total). Also good to check FBC, ferritin, folate, LFTs, Calcium, prothrombin time.

“HLA typing is not required in patients with positive TGA-IgA, if they qualify for CD diagnosis with
biopsies or if they have high serum TGA-IgA (>=10x ULN) and EMA-IgA positivity. If a patient tests negative for HLA DQ2 and DQ8, the risk of CD is very low, while a positive result does not
confirm the diagnosis.”

“Recent studies suggest that the no-biopsy approach to diagnose CD can be applied in asymptomatic children. In asymptomatic children, however, the PPV of high TGA-IgA >=10x ULN may be
lower than in symptomatic children, which needs to be considered during the decision-making process”

  • Positive tTG alone is insufficient for diagnosis, and should not be a reason for gluten free diet.
  • If tTG is high but less than 10x upper limit, then proceed to duodenal biopsy.
  • If tTG more than 10x upper limit of normal, alternative to biopsy is to check IgA EMA and do HLA DQ2/8 screening. If BOTH positive, diagnosis is confirmed. If EMA not available, a second strongly positive tTG is an acceptable alternative (but save serum for EMA testing at future date).
  • If IgA deficient, use IgG tTG or EMA, but less specific so low threshold for biopsy.

Note that antibodies may be false negative if the diet is low in gluten at the time of testing. So normalize gluten intake (at least 2 meals per day, for at least 6 weeks) but discuss with specialist if clinical condition so poor that treatment cannot be safely delayed.

False positives also occur, so diagnosis must be confirmed by endoscopy (or another diagnosis may become apparent). Endoscopy for high risk symptoms (diarrhoea, wt loss, anaemia) and serology is 100% sensitive for coeliac. But a proportion with high risk symptoms and positive serology do NOT have positive biopsies! Cause? Perhaps atypical disease (ie no GI symptoms) is actually more common than typical! Consider the incidences of anaemia, infertility, short stature, unfavourable pregnancy outcomes…

Screening

Coeliac disease is associated with other conditions, which may justify screening:

  • Type 1 diabetes (8%)
  • IgA deficiency (up to 7%)
  • Downs, Williams and Turners syndromes!
  • Autoimmune thyroiditis
  • Autoimmune liver disease
  • Unexplained abnormal LFTs
  • Relatives of coeliac disease patient (10% in 1st degree relative)

Before testing, discuss relative risks of untreated coeliac disease (osteoporosis, infertility, small bower cancer), and the need for biopsy and gluten free diet if tests are positive. Then test:

BSPGHAN say check HLA DQ status and IgA tTG.  NICE says do not use HLA DQ2/8 in non-specialist settings, but consider if not proceeding to biopsy or those on low gluten.

  • If HLA DQ2/8 neg, then v unlikely.
  • If DQ pos but tTG neg, then unlikely (unless IgA deficient or on low gluten diet). Still potential to get disease later in life, so test again in 3yrs or if symptomatic.
  • If DQ/tTG pos but tTG less than 3x upper limit of normal, then do IgA endomysial antibody (EMA) and proceed to biopsy if positive. If EMA negative, continue to monitor.
  • If DQ pos and tTG higher than 3x, biopsy. (Although option is given to retest in 3-6 months)
  • If IgA deficient (<0.07mg/L), consider using IgG EMA, deamidated gliadin peptide (DGP), or tTG
  • Have a low threshold for retesting if signs/symptoms consistent!

Biopsy

Villous atrophy on biopsy (do 4) is characteristic. Marsh grading system: infiltrative changes with crypt hyperplasia is compatible, positive serology strengthens diagnosis. If diagnosis still uncertain, consider HLA testing as above, repeat biopsy after increasing gluten intake or else go the other way, and biopsy after gluten free diet!

Biopsy if gluten excluded and persistent high titres at 12 months or persistent symptoms.  Serological tests alone not adequate to determine if gluten has been excluded!

Treatment

The benefits of treatment, in symptomatic children are:

  • resolution of symptoms,
  • reversal of bone demineralisation,
  • Resolution of micronutrient deficiencies and probably better height gain
  • less delayed puberty, menstrual problems, subfertility, spontaneous abortions and LBW babies
  • decreased risk of some intestinal cancers, to normal levels (T cell lymphoma, Ca oes/pharynx).  T cell lymphoma risk falls to baseline after 10 years gluten free diet
  • Possible prevention of associated autoimmune conditions (evidence conflicting) – see below

In asymptomatic patients, there are no long term studies as yet to show benefits so need to discuss with family.

Diet

Food labelling allows up to 200ppm gluten in gluten-free foods: some people may be sensitive at lower levels than this (at least, their mucosa may be sensitive – they may remain asymptomatic). Gluten free foods are available on prescription.

Oats are safe for 95% of patients (besides contamination issues and the above food labelling problem). Ideally exclude initially and consider reintroduction (products marked gluten free) when well eg at 1yr; normalization of tTG and continued low titres reassuring!  NICE says can be included at ANY stage, but review immunological/clinical/histological response.

Most coeliac patients can tolerate wheat starch and malt extract but not all.

Follow up

If compliant on diet, antibodies should go negative within a year. The mild transaminitis commonly seen at diagnosis should resolve – if not, and on diet, then consider Autoimmune Hepatitis. Complete mucosal recovery can take years.

Monitor symptoms, growth, puberty, antibodies (eg 6 monthly, then 12-24 monthly). Poor clinical response = poor compliance! TTG, FBC, Ca/Phos/ALP, Ferritin, Vit B12, folate, Vit D, PTH, TFTs.

Consider bone scan – see osteoporosis

Discuss oats, as above.

Pneumococcal vaccine recommended.

Transition

Understanding of diagnosis, antibodies.

  • Encourage maturation of communication and decision-making skills.
  • Allow patients to take responsibility for medical self-management.
  • Help the patient develop healthy habits and self-care skills that encourage autonomy eg smoking, exercise, alcohol/drugs
  • Education and counselling re: gluten-free diet (food on prescription, nutritional completeness, healthy weight) and consequences of non-adherence.
  • Recognition and treatment of psychological/emotional issues eg : discouragement, feeling overwhelmed, anxiety about the future and complications such as depression and eating disorders.
  • Familiarize young person with healthcare system

For those patients with significant pubertal delay, paediatric provider may be better suited to provide guidance until transition to an adult provider at the completion of puberty.

Topics for discussion –

  • How there can be a long interval between gluten exposure and the return of symptomatic disease.
  • How coeliac disease can interfere with school, education and work (eg military service)
  • Sexuality and fertility (women with untreated CD are more likely to suffer an adverse pregnancy outcome) – lifetime fertility however is similar in individuals with and without coeliac
  • Adolescents report lower adherence than younger children, esp at social events. Dietary non-adherence is associated with poorer QoL and increased physical symptoms. Most young people with CD think that avoiding cancer is the most important reason to adhere to diet, but the risk for cancer is much lower than previously presumed, so osteoporosis and adverse pregnancy outcome may be bigger issues.
  • Risk of passing it on to children.
  • Associations with diabetes, thyroid disease, autoimmune liver disease.

Primary care may be a suitable care provider.

[Prague consensus, Ludvigsson Gut 2016;65:1242-1251.]

Coeliac UK support group

Mediation

Generic

Has to be voluntary to work! Do both parties want resolution?  Can they express reasons for discomfort/distress?  Can mediator control and sustain process (needs to be safe)?  Are all parties committed to keeping agreement in long term?

“Everybody does that” – groups allow individuals to fail to take responsibility for behaviour.

Ideally fix teams before getting to point of mediating between 2 (or more) individuals!

Issues typically:

  • inequity/fairness
  • annoyance
  • hurt (esp respect, valued)
  • disagreements (even though healthy!)
  • competition

Good attention – focus, openness, impartiality, caring, withholding judgment.

Stages – before meeting face to face.

  1. Tell story, compare before and after, what changed?  But acknowledge qualities in others (start to shift thinking!).  Define issues.
  2. What could a future look like?
  3. How do we get there?  What is most important to you?  What could you live with?  Honesty essential!

Then write introductory statement before sitting down face to face.

(Andrew Graham, Diane Swanson)

Values based reflective practice

Generic

VBRP (Michael patterson)

Reflection vs quality control, reporting back to management!

Bitching=reflection without looking to future!

Should be a process of turning history into learning.  Purpose is to reflect on practice, with a view to fostering habit of reflecting IN practice.

Start is traditionally with Actual Practice.  VBRP starts with Motivations (Soul and role, vision and values.  Why bother!?).  Sorting that out tends to deal with problem of quality control!  From Actual practice, then to Potential practice.

Needs conducive environment cf patronising, judging, analysing.  Else survival but not learning.

2 tools available – 3 levels of seeing, and NAVVY.

3 levels of seeing

•    Observe without interpreting (don’t hold back!)
•    Questioning/curiosity (I wonder…  Do you ever…)
•    What do you think now? (Penny drops – perception, realization)

Offensively simple, but hard to do without diving in.

NAVVY

•    Needs – whose needs were met?  Not met?
•    Abilities – what does situation tell us about abilities/capabilities?
•    Voice and power – Who was heard?  Not heard?
•    Values – what was undervalued?  Overvalued?
•    You – what does situation say about you/me/us?

What’s the matter with you? cf What matters to you?

“Nothing about me, without me” (mental health)

Can be applied to ward rounds, MDT, training/education, service delivery etc etc

Research has shown increased motivation, satisfaction, confidence and reduced stress.  Even better team communication (shared values?).