Niemann Pick disease

General paediatrics, Metabolic, Neurology, Respiratory

Sphingomyelinase (lysosome) disorder.  Type B has only visceral involvement, can survive into adulthood.  More common in Ashkenazi Jews.

Typically develop symptoms at around 6 months.  Can be prolonged jaundice as baby, else abdominal distension (hepatosplenomegaly), growth failure, hypotonia, failure to meet milestones.

Death usually around 3yrs, recurrent lung infections, interstitial lung disease.  Spasticity develops later.

Cherry red spot seen on fundoscopy in macula, possibly not in early stages.

Rheumatic fever

Cardiology, Clinical, General paediatrics, Immunology, Infectious disease, Microbiology, Rheumatology

Rare in developed world now, still common in underdeveloped world, or at least in underdeveloped communities eg Aboriginal Australians.  Prob also genetic susceptibility.

Autoimmune, multisystem disease triggered by Group A streptococcus infection.  Important cause of acquired heart valve disease. 

Can recur.

Probably cross reactivity between specific Group A strep M proteins and human tissues.

Erythema marginatum
Erythema marginatum

Diagnosis

Jones criteria:

  • Major
    • Carditis eg new murmur.  Mitral most commonly, classically apical blowing pan-systolic.  Aortic next most common.
    • Arthritis esp large joints.  Migratory.
    • Subcutaneous nodules – these are the most uncommon major criterium (in Turkish study of over 1000 cases there were none with nodules).  Typically over extensor surfaces of joints, 0.5-2cm, symmetrical.
    • Sydenhams chorea
    • Erythema marginatum – not specific to rheumatic fever. Seen in 0.4% of Turkish study patients. Serpiginous or annual eruption, can look similar to erythema multiforme. Provoked by warmth eg bath.  Non pruritic.
  • Minor
    • Fever
    • Arthralgia
    • Prolonged PR interval on ECG
    • Elevated CRP/ESR
  • 2 major or 1 major plus 2 minor, plus confirmation of group A streptococcal infection eg positive culture, high ASO titre sufficient for diagnosis. Modified Jones takes into account background incidence.

Note that initial infection may be subclinical eg pharyngitis, erysipelas. Symptoms of rheumatic fever develop 10 days to several weeks later. Chorea can appear months later.  Low threshold for echo as carditis can also be subclinical.

Established criteria for rheumatic valvulitis – Gewitz 2015

Treatment

Antibiotics – Treat with penicillin,  this does not however affect clinical course but hopefully prevents further spread of that particular bug. Traditionally single dose intramuscular Penicillin G Benzathine.

NSAIDs for joint pain.  Usually dramatic response, if not then reconsider diagnosis!

Valproate for chorea, possibly steroids – see Sydenham’s.

Aspirin and/or Steroids for carditis, but not much evidence.  Diuretics, ACE inhibitors for cardiac failure.

Long term treatment

Recurrence with progression of valve damage is the main concern, and well recognized. Subclinical carditis improves in about 50% but definite risk of progression (mild definite and borderline RHD showed 26% and 9.8% echocardiographic progression respectively).

Regular intramuscular penicillin (benzathine pencillin G) every 2-3 weeks has the lowest recurrence rates but oral penicillin V more acceptable.  Erythromycin or cephalexin if allergic.

WHO recommendations:

  • Rheumatic fever without carditis: 5 years after last attack or until age 18 (whichever is longer)
  • Rheumatic fever with carditis but without residual disease: 10 years after last attack or until age 25 (whichever is longer)
  • Residual valve disease or valve replacement: lifelong

American and Australian heart association guidelines vary slightly:

Penicillin prophylaxis guidelines comparison

Seizures

Clinical, Emergency medicine, General paediatrics, Neurology, OPD

Seizures, fits, funny turns, convulsions, attacks…  None of these really has a medical meaning.  Convulsion suggests rhythmic motor activity, but that’s about it.  The implication of most of these is that there is excessive abnormal, involuntary muscle contraction, usually bilateral.  But more broadly, some involuntary, usually sudden and self terminating episode of abnormal (or at least non-purposeful) activity and/or impaired awareness. Can be sustained or interrupted.

Nottingham RCPCH approved guideline distinguishes:

  • Febrile?
  • Already on anti-epileptic medication?  Consider checking levels, or at least storing sample.
  • Predisposing conditions? eg neurodevelopmental problem, brain injury/surgery.
  • Neonate or young infant? Some additional possibilities eg hypoxic ischaemic encephalopathy (HIE), Fifth day fits, drug withdrawal (neonatal abstinence syndrome), pyridoxine dependent epilepsy.

Most commonly Febrile convulsions ie age related, benign.  Beware complex (multiple seizures in same illness, focal features, prolonged >15 mins) and any abnormal findings eg neck stiffness, bulging fontanelle, prolonged illness, abnormal cognition before/after.

Important differentials are:

  • meningitis
  • encephalitis
  • shaken baby (non-accidental injury)
  • brain tumour/haemorrhage, hydrocephalus
  • ingestion (deliberate or accidental)
  • metabolic (low glucose, calcium/magnesium, low/high sodium)

May represent first evidence of epilepsy.

Family centred ward rounds

Communication, Generic, Patients

A study highlighted that the attending physicians talk outside the room as much as or more than they do inside the room.

“It is frustrating to hear the team speaking about you in the hallway before they come in and wondering what they are saying. Then, after they leave the room, they continue to have discussions in the hallway, where we can hear pieces and parts but not all of the discussion.

“We would prefer that all discussion happen in the room with the nurses and the family present.”

The nurses are the ones who have spent the most time with the family, and they have a lot of information to offer. However, the study highlighted that the nurse does not have much of an opportunity to speak during the rounds.

Sometimes, the entire rounds process is effectively over by the time the medical team comes into the room, and rounds are more of a procedural event than a discussion.

Other comments from one family:

  • It would be nice if all physicians involved in the care could participate in the family-centered rounds experience, even if some need to be on the phone. Many times, the rounding process happens but then we are left with a statement that they will wait until the other doctors come by to make a decision. This not only prolongs the decisions but also splinters the care that the concept of family-centered rounds is trying to improve.
  • We appreciate when the medical teams sit down in the room with us. It makes us feel as if we are having a discussion where everyone is invited to participate instead of a group of people standing over us. This style of communication seems to engage the patient and family in honest, open conversation, and it seems to cause the team to slow down enough to listen to our story.
  • It would be nice to have some idea of when they are coming to the room because it seems that no matter what we do, the team comes in when one of us has run to the cafeteria to get breakfast or to take a phone call in the lobby.

[Sarah Pickel, Mark W. Shen, Collin Hovinga.  Hospital Pediatrics  Jul 2016,  6  (7)  387-393;  DOI: 10.1542/hpeds.2015-0136]

Patient centred care

Communication, Generic

As seen in previous studies of medical students, junior doctor patient-centred attitudes declined during their first year of residency.

There is a clear gender gap.  Female residents were generally more inclined to a patient-centred attitude. The difference by gender was more evident for the caring component than the sharing component.

Male residents became less patient-centred in terms of caring attitude after 1 year, while female residents showed little decline.

A previous meta-analysis indicated that female physicians are more likely to address psychosocial issues, use emotional talk and positive talk, and more actively incorporate patient input.  All of this could be considered patient centred.

Role models tend to be same gender, which perhaps explains why male doctors tend to learn patriarchal styles.

Interestingly, physicians’ confidence in communicating with patients increases more in those who showed a smaller decline in patient-centred attitude.

[BMC Med Educ. 2018; 18: 20.         doi:  10.1186/s12909-018-1129-y]

See also Family centred ward rounds.

 

Horner’s syndrome

Clinical, General paediatrics, Neurology

Horner’s syndrome = small pupil, ipsilateral ptosis +/- reduced sweating.  Compare Holmes Adie pupil.

Anhidrosis localizes lesion to preganglionic branch.

Turn down the lights to make it more obvious!  Look for associated Klumpke’s.

In babies usually congenital or related to birth trauma, rarely it can be due to:

Other cranial nerve involvement clearly points to brainstem problem.

[British Journal of Ophthalmology 1998;82:51-54. ]

Complement

General paediatrics, Immunology, Infectious disease

C3 and C4 are measured at the same time since this gives an indication of the complement pathway (classical or alternative) which is being activated and thus the cause of this activation.

C3 alone is often decreased in infectious disease (septicaemia, endocarditis), so not v interesting if isolated, unless concern about immunodeficiency (see below).

C4 alone is characteristically decreased in hereditary angioedema, can also be immune complex diseases particularly vasculitis, and in cryoglobulinaemia and cold agglutinin disease. Immune complex diseases can lead to consumption of both C3 and C4, with low levels.

Measurement of serum complement is useful in the monitoring of specific immune complex diseases eg SLE, post streptococcal disease, subacute bacterial endocarditis. Consumption of one or both components may also be useful prognostically eg nephritis in lupus.

Deficiency

Complement deficiency is a type of immunodeficiency.  Though genetic C3 deficiency is v rare, deficiencies in other components (which are more common, though still very rare) can result in low C3.  CH50 or CH100 are better tests of whole pathway.

Genetic deficiencies in C4 are rarely detected.

Notifiable diseases (Scotland)

General paediatrics, Infectious disease, Microbiology

Public Health etc Act Scotland 2008

There are notifiable diseases and notifiable organisms:

Notifiable diseases

  • Clinical syndrome due to E.coli O157 infection
  • Haemolytic Uraemic Syndrome (HUS)
  • Necrotizing fasciitis
  • Severe Acute Respiratory Syndrome (SARS)
  • (plus infections caused by organisms below)

Notifiable organisms

  • Bacillus anthracis (anthrax)
  • Bacillus cereus
  • Bordetella pertussis
  • Borrelia burgdorferi (Lyme disease)
  • Brucella genus
  • Campylobacter genus
  • Chlamydia psittaci
  • Clostridium botulinum (Botulism)
  • Clostridium difficile
  • Clostridium perfringens
  • Clostridium tetani
  • Corynebacterium diphtheriae (toxigenic strains)
  • Corynebacterium ulcerans
  • Coxiella burnetii
  • Crimean-Congo haemorrhagic fever virus
  • Cryptosporidium
  • Dengue virus
  • Ebola virus
  • Echinococcus genus
  • Verocytotoxin-producing E.coli (VTEC)
  • Francisella tularensis
  • Giardia lamblia
  • Guanarito virus
  • Haemophilus influenzae type b (from blood, cerebrospinal fluid or other normally sterile site)
  • Hantavirus
  • Hepatitis A-E virus
  • Influenza virus (all types, including those caused by a new sub-type)
  • Junín virus
  • Kyasanur Forest disease virus
  • Lassa virus
  • Legionella genus
  • Leptospira genus
  • Listeria monocytogenes
  • Machupo virus
  • Marburg virus
  • Measles virus
  • Mumps virus
  • Mycobacterium bovis
  • Mycobacterium tuberculosis complex
  • Neisseria meningitidis
  • Norovirus
  • Omsk haemorrhagic fever virus
  • Plasmodium falciparum, vivax, ovale and malariae (malaria)
  • Polio virus
  • Rabies virus
  • Rickettsia prowazekii
  • Rift Valley fever virus
  • Rubella virus
  • Sabia virus
  • Salmonella (all human types)
  • SARS-associated coronavirus
  • Shigella genus
  • Enterotoxigenic Staphylococcus aureus
  • Staphylococcus aureus (all blood isolates)
  • Methicillin-resistant Staphylococcus aureus (MRSA)
  • Streptococcus pyogenes (from blood, cerebrospinal fluid or other normally sterile site)
  • Streptococcus pneumoniae (from blood, cerebrospinal fluid or other normally sterile site)
  • Toxoplasma gondii
  • Trichinella genus
  • Varicella-zoster virus
  • Variola virus
  • Vibrio cholerae
  • West Nile fever virus
  • Yellow Fever virus
  • Yersinia enterocolitica
  • Yersinia pestis
  • Yersinia pseudotuberculosis

Polycystic ovary syndrome (PCOS)

Endocrinology, General paediatrics, OPD

Now (2026) PMOS – polyendocrine metabolic ovarian syndrome. Takes focus off the ovarian cysts, which are not always seen, often seen incidentally, and probably the least relevant thing about it.

No single test. Also operator dependent esp teens.

  • Hirsutism (even male pattern baldness), But NOT virilisation (eg clitoromegaly, voice changes, musculature).
  • acne (moderate to severe),
  • irregular periods.  Can be amenorrhoeic, dysfunctional uterine bleeding, infertility but 20% have normal cycle.
  • Obesity (35-50%, not all),
  • Acanthosis nigricans.

Insulin resistance is associated, and obviously presents the most important long term risk. Acanthosis nigricans is highly associated with insulin resistance, family history of type 2 or gestational diabetes a clue.

Differential includes pregnancy, hypothyroidism, hyperprolactinaemia (mild hyperprolactinaemia commonly seen in PCOS, transient), late onset Congenital Adrenal Hyperplasia (CAH), ovarian/adrenal tumour, Cushing syndrome.

Investigations

  • LH/FSH – ratio often high (3:1 or more) but inconsistent so not considered diagnostic
  • Testosterone can be high (up to 4.8) – if higher, suggests alternative diagnosis
  • Free androgen index (=testosterone x100/SHBG) can be high but our lab only calculates for adults – reference range of up to 7
  • SHBG – low in PCOS (and in obesity, hypothyroidism, hyperprolactinaemia). Plus marker of insulin resistance),
  • Prolactin, 17OH Progesterone for differential
  • Fasting glucose/insulin ratio (under 4.5=insulin resistance, up to 7 in adolescents), glucose tolerance test, lipids.

No normal range for hormone tests in pubescent girls, so these only give a vague suggestion of an underlying issue.

Given there is no specific treatment, try not to focus on making the diagnosis (with attendant self image issues etc), but concentrate on managing symptoms (for young people, heavy irregular periods and hirsutism; for adults, infertility) and long term risk viz diabetes and cardiovascular disease.

Note that less than 4 menses per year has higher risk of endometrial cancer.

Consider:

  • oral contraceptive pill (OCP) – progesterone only, or combined, or else 12 week cycles of medroxyprogesterone acetate 5mg BD followed by 1 week break – NOT contraceptive!
  • Metformin
  • Spironolactone (has anti androgen effect)
  • Plucking/shaving/electrolysis/laser, eflornithine cream
  • Clomiphene for fertility.

[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1069067/]

Congenital Syphilis

Congenital, General paediatrics, Infectious disease, Microbiology, Neonatology

In US primary, secondary and cong syphilis all surged in the 90s, now focal outbreaks in urban, drug using population. In N Africa, 3% of pregnancies, up to 7% in Carribean. 1 million pregnancies affected worldwide, of which 50% will end in abortion or still birth, and the other 50% will be congenital cases (unlike TORCH).

Clinically, 2/3 affected neonates asymptomatic at birth. Otherwise:

  • “snuffles” (vesicles on upper lip, highly infectious)
  • mucous patches (moist erosions)
  • hepatosplenomegaly and hepatitis
  • anaemia +/- hydrops
  • meningitis, with CSF pleocytosis and high protein
  • pneumonia, +/or fluffy diffuse infitrates on CXR (=pneumonia alba)
  • pseudoparalysis

Years later:

  • Typical facies – frontal bossing, saddle nose, short maxilla, high palate
  • Mulberry Molar (5 blobs in ring shape to tooth, pathognomic!). Hutchinson’s incisors (peg-like) better known.
  • Gummata (rubbery ulcers)
  • Sabre tibia (anterior bowing)
  • Hutchinson’s triad = interstitial keratitis, peg shaped incisors, and sensorineural deafness.

Prevention

The risk of transmission is very high, particularly for untreated primary (ie a chancre) or secondary (ie multiple lesions, lymphadenopathy) disease. The risk falls to 40% for early latent syphilis (ie test positive but asymptomatic, with infection likely to have occurred in the previous 12 months on the basis of previous tests, symptoms or exposure). A category exists of latent syphilis of unknown duration, which only applies to patients aged 13-35yrs with nontreponemal titre of 32 or more.

Treating syphilis in pregnancy – for early acquired disease (primary, secondary or latent of <1yr) benzathine penicillin 50 000U/kg, with second dose a week later if in third trimester [BNF] but exclude neuro. For late latent syphilis >1yr duration give 3 doses at weekly intervals. For neuro disease benzylpen 50 000U/kg qds for 10-14/7 followed by 3 doses benzathine penicillin as above. If HIV positive also, then there tends to be more CNS disease, treatment failure, and treatment reactions (fever, myalgia, preterm labour – give steroids).

Adequate antenatal treatment = adequate benzathinepenicillin dose (2.4M Units IM) once weekly x3 – erythromycin is not reliable), 30 days before birth, proven 4x drop in nontreponemal serology.

Diagnosis

Syphilis tests are either nontreponemal or treponemal.

  • Nontreponemal viz VDRL, RPR are screening tests, 70% sensitive in primary, 99% in secondary.
    • False positives – lupus, infection, recent immunization, pregnancy, other treponemes.
    • Quantitative – correlate with disease activity: 4x rise in titre early on or in relapse, drop of 4x suggests adequate response to treatment. In secondary, titres are always high ie 1:32.
    • False negative – early? Tertiary – V high levels of antibody! So if high suspicion then do dilutions.
    • Should become negative within 1 yr of treatment in primary, 2 yrs in secondary or congenital, 5 yrs in late.
  • Specific treponemal tests eg TP immobilization (TBI), fluorescent T antibody absorption (FTA-Abs) used to confirm.
    • False positive with non pallidum, Lyme or other borrelia.
    • Remain positive for life, even with treatment.
    • Do not correlate with disease activity.
    • FTA-Abs IgM available for testing baby, but still has false positives/negatives

In newborns, direct microscopy and fluorescent antibody tests can be done from mucous patch, else from placenta (beware non pallidum treponemes in normal flora esp mouth). PCR can be done from lesions too. VDRL more than 2x dilutions richer than mum’s is suggestive. IgM can be negative early esp infection occurring late in pregnancy, not always recommended. False positive VDRL may occur due to transplacental antibodies if high maternal levels.

Where disease is likely, or maternal treatment has been inadequate, further testing is required:

  • FBC, LFTs
  • Lumbar puncture, incl VDRL on CSF (not 100% sensitive so if congenital disease suspected, treat for neuro.)
  • XR long bones to look for destructive lesions. Even in asymptomatic, XR changes seen in 20% esp ankles, knees but also wrists, elbows. Lesions are symmetric, multiple: periostitis, osteitis, osteochondritis.
  • CXR
  • Ophthalmology assessment

For screening adults, 1 step strip test available, and one off oral treatment (Azithro, 1.8g). Antibodies give only partial protection.

Treatment

For congenital syphilis treat with benzylpen 100-150 000 U/kg/d in bd or tds doses for 10-14/7.

There is concern about CSF levels with procaine or benzathine penicillin, although sometimes these are used for asymptomatic babies with nontreponemal tests less than 4x mum’s, which might occur with inadequate treatment. In this situation, any abnormal finding on evaluation requires full 10/7 course.

If late diagnosis (>4/52), give high dose viz 200-300 000 U/kg/d qds for 10-14/7. If CNS disease is excluded, this could be converted to benzathine penicillin.

Follow up

Monitor to show fall in VDRL at 3-6 months.

(Rana Chakraborty, St George’s)