Muscular Dystrophy

Dystrophin is largest gene in body – prone to duplications/deletions. Large errors can be picked up quickly on testing. Point mutations (30%) takes more sequencing work.

Duchenne MD is X-linked but girls can get symptoms. Life expectancy was 18-20 yrs but now with steroids and non-invasive ventilation, 40 plus.

Different natural history trajectories identified – makes trials hard, as not comparable…

Becker muscular dystrophy is similar but less severe. Other muscular dystrophies include myotonic dystrophy, Emery-Dreifuss muscular dystrophy, facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophies, and congenital muscular dystrophies. Spinal muscular atrophy related. Management of all similar.

Diagnosis

Often delayed. Classically delayed motor milestones, frequent falls, abnormal gait, muscle pain; but sometimes speech and language delay, learning difficulty more prominent. Urine/bowel issues. Later difficulty with jumping, running, climbing steps, and rising from the floor.

Leg flexors tend to stay strong cf extensors – leads to lordosis and contractures, and classic posture where weight forward to avoid jack knifing.

Calf hypertrophy classic. Tone and reflexes reduced (cf cerebral palsy).

Gower’s sign – using hands/arms to get up from floor and to standing position

Creatine kinase levels are elevated. Diagnosis is confirmed by genetic testing.

If CK normal, then EMG and muscle biopsy required.

Treatment

Lung function should be monitored.

Steroids are recommended from diagnosis. Preserves ambulation, respiratory function (delays the need for mechanical ventilation); avoids/delays scoliosis surgery; delays onset of cardiomyopathy; increased survival.

ACE inhibitors recommended to delay onset of cardiomyopathy.

Gene therapy difficult because of size of gene and problem of packing into vector!

Lots of trials. Givinostat approved by FDA – old drug for JIA! – conditional license in UK, early access programme in UK. Vamorolone is steroid, potent but less side effects eg bone/growth – now recommended by NICE (January 2025).

FDA has approved first gene therapy treatment – but have been fatalities and effect over time unclear.

Ataluren – oral – but EMA have withdrawn license due to poor efficacy.

Family Support

Muscular Dystrophy UK

[Zoya Al-Haswani – Heartlands Hospital]

High flow treatment

=Heated humidified oxygen.

Turn machine on at least 15 minutes before use (else high flow COLD air, which is not good).

No battery pack, so can’t move for intubation!

Flow rate depends on size of baby – basically 2l/kg/min, or 12l/min from 6kg. Maximum flow is 20 if over 6kg, no scope for increase below that.

Start at 40% FiO2. Increase if saturations below 94%, increase flow if persistent/worsening work of breathing or resp/heart rate.

Response usually within first few hours – if none then likely intubation required.

Weaning

Wean FiO2 in steps of 5% every hour.

Once under 30%, wean flow by 2l/min every 2 hours.

Reintroduce feeds if FiO2 below 40%.

Discontinue treatment once flow down to 4.

Atypical mycobacterial infection

Classically a cold abscess, usually in the neck. Ingested soil?

Overlying skin can become discoloured, and ultimately fistulation may occur. Child is usually systemically well.

Blood tests are normal. Mantoux testing can be positive due to cross reaction with BCG. Fine needle aspiration may be most appropriate.

Drug treatment needs to be prolonged and recurrence is common.

Surgery can be tricky.

Grave disease

Graves usually 10-20yrs at presentation. 6:1 female. Usually family history of thyroid or other autoimmune disease. Insidious else acute. Palpitations, diarrhoea, heat intolerance, agitation and deteriorating school performance, weight loss. 

Tremor, fidgety, hypertension, goitre (diffuse, smooth), bruit, exophthalmos (rare in kids). Storm can be triggered by infection or non-compliance. Hyperpyrexia, tachycardia. 

Differential

Neonates can get transient hyperthyroidism driven by maternal antibodies – improves after a few months.

Besides Grave disease, other causes of hyperthyroidism are solitary thyroid nodule (adenoma), multinodular goitre, TSH receptor abnormalities. 

Diagnosis

Besides TSH, do free T4 and T3. FT3 useful (T4 can be normal!) for showing T3 thyrotoxicosis (usually due to toxic nodular hyperthyroidism or early Grave).

Thyroid receptor antibodies usually positive. Do TPO also.

Treatment

Carbimazole – Usually 24 months total, TFTs normalise within 12/52 and dose can then be reduced.  Neutropenia as idiosyncratic side effect (so FBC monitoring not helpful!). If mild stop temporarily. Propylthiouracil second line (liver failure, ANCA vasculitis)

Radio-iodine – avoid <10yrs. Can have storm. Need long term thyroxine. 

Surgery – total or near total excision. Risk of malignancy in remnant. Esp large gland. Hypoparathyroidism as transient side effect. Recurrent laryngeal nerve damage. Iodide used pre-operatively to help texture!

Propranolol short term e.g. 3-4 weeks

Block and replace strategy – where you add thyroxine rather than reduce carbimazole? But 2 drugs not 1!

Relapse common, 2/3 within 2yrs, in adults remission unlikely after 2 years but not true in kids. 

Malignancy risk higher in Grave regardless of management…

Proctalgia

=anal pain.

Rule out anal fissure (may be hard to see but bleeding or sentinel pile are clues, typically caused by constipation), thrombosed haemorrhoid, infection.

After that, functional (see Rome criteria)- often triggered by defaecation or sitting.

Classifed as acute (less than 20 mins – “fugax”) or chronic (greater than 20 mins episodes). Latter thought to be due to paradoxical pelvic floor contraction.

Biofeedback has best evidence but consider tricyclic antidepressants, Botox, and sacral nerve stimulation (!).

Testosterone

Should be only low levels until puberty kicks in.

Most of the research into testosterone and aggression comes from adults.

Some small studies have found a link between testosterone levels in children and aggression, particularly in boys, but not all. Similarly some studies have suggested low cortisol in association with aggression, but other studies have found links to high cortisol.

A small study of pre pubertal and pubertal children (boys and girls) found testosterone levels were associated with high moodiness and low attachment. Testosterone was also associated with low sociability, but only in the prepubertal group. 

One study suggested that the influence of these hormones can modulate the balance of aggressive tendencies and empathy, with cortisol being relevant only to boys and testosterone only to girls.

All these studies at high risk of bias.

Primum non nocere

“First do no harm” – fundamental of medical ethics.

Except dubious origins… The Latin makes people think it’s Hippocrates and in the Hippocratic oath – but Hippocrates was Greek and it’s not in the oath. He does say something pretty similar in the Epidemics.

Not in the Oxford English Dictionary. Well known in America in the 1930s.

1860 Medical Textbook by Inman says it comes from Thomas Sydenham, but not found in his work, and no one else confirms this. But Sydenham did like Latin.

Florence Nightingale says it in English in the preface to her book on hospitals but not in Latin.

Jack Eckert reckons it was the Latin versions of Hippocrates that started to circulate as printed versions that gave rise to the expression. But still odd that rarely used in either English or Latin until second half of 20th century.

Of course, it isn’t a great principle in any case. Most of medicine is a risk:benefit calculation, rather than avoidance of any possible harm.

Lots more discussion in Cedric Smith’s article.

Scabies

Serpiginous burrows between the fingers, in the flexures of the wrist, genitalia etc characteristic but rare. More usually papules, pustules – pruritus often on unaffected skin and esp at night. In infants, lesions on head, nappy area, occ palms and soles.

Caused by the mite sarcoptes scabiei, which does not fly or jump – direct skin contact, mostly. Infection by contact with fomites is very rare.

Rash is partly hypersensitivty so not related to number of mites, may take several weeks after inital infestation to appear – on reinfection just a few days. Cross reaction with related house dust mite.

Topical steroids will mask rash/itch. Superinfection common. Differential is contact dermatitis, animal scabies (do not form burrows, do not complete life cycle so self limited), lichen planus.

Rarely, nodular form (esp groin, axillae) – hypersensivity reaction. 

Norwegian or crusted scabies esp immunosuppressed (but not necessarily) – psoriaform, not always itchy, very infectious.

Treat with Permethrin 5% (=Lyclear) dermal cream [Permethrin 1% rinse cream ineffective in scabies cf head lice]. Safe in infants (rarely CNS side effects). An alternative treatment is Malathion (safe in pregnancy). All household members should be treated simultaneously. After treatment the itching from scabies can take weeks to settle. Treatment should be extended to the scalp, neck, face and ears in children up to the age of 2 years. All skin surfaces should have the agent applied for 24 hours for malathion and for 8-12 hours for Permethrin 5% and have treatment repeated at 7 days.

Oral ivermectin in single dose is effective in over 70%, given twice 2 weeks apart 95% effective. Use for crusted (along with keratolytics), epidemics. Lancet Infectious Diseases Volume 6, Number 12, December 2006

HACEK organisms

Group of similar gram negative, low pathogenicity organisms – not actually related to each other, but cause similar infections:

  • Haemophilus (usually parainfluenzae, not H. influenzae which rarely causes endocarditis)
  • Aggregatibacter actinomycetemcomitans (prev Actinobacillus)
  • Cardiobacterium hominis
  • Eikenella corrodens
  • Kingella kingae

Commensals of the mouth – usually just cause dental infections but can cause endocarditis (gram positives are the usual cause) and osteomyelitis (esp Kingella – named after Elizabeth King – can be spread by respiratory route, so outbreaks of septic arthritis!).

May grow on chocolate agar but not the McConkey you usually use for gram negatives. Some beta-lactamase but most susceptible to cefalosporins.