Category Archives: Rheumatology

Ehlers-Danlos syndrome

June 19, 2015General paediatrics, Genetics, Orthopaedic, Rheumatologyvascularadmin

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.

Haemophagocytic syndromes

March 23, 2015General paediatrics, Haem/Oncology, Immunology, Rheumatologyadmin

A group of disorders, including haemophagocytic lymphohistiocytosis, Macrophage activation syndrome, and PIMS-TS. Suspect when these unexplained or unusually severe, particularly in combination:

persistent or intermittent fever
elevated or rising ferritin or other inflammatory markers (CRP, LDH)
splenomegaly (eventually hepatosplenomegaly)
inappropriately low or falling haemoglobin, platelets or white cells (neutrophils and lymphocytes) -evolving into severe pancytopenia
coagulation abnormalities (in particular, hypofibrinogenemia, increased D-dimers, even DIC)
hepatic dysfunction including high triglycerides
CNS dysfunction (including seizures and encephalopathy, with raised CSF protein)

The underlying problem is the inability to kill infected target cells. The frustrated NK-l and cytotoxic T-cell activity leads to a massive inflammatory cascade, resulting in macrophage activation, dissemination, and organ infiltration. The haemophagocytosis of the name refers to characteristic macrophage/histiocyte consumption of erythrocytes, most evident in the marrow but sometimes seen in the peripheral blood film. Not always dramatic, not always evident at presentation so serial bone marrow examinations may be required (spleen aspirate?).

There are four categories:

a familial syndrome (perforin deficiency)
associated with infection (Epstein-Barr virus, cytomegalovirus, parvovirus B19, bacteria, fungi, mycobacteria, and parasites)
associated with juvenile idiopathic arthritis (where it is usually called macrophage activation syndrome)
associated with immunodeficiency
- DiGeorge syndrome should be excluded by FISH
- Lysinuric protein intolerance – hyperammonemia is characteristic
- the accelerated phases of Chediak-Higashi and Griscelli syndromes (both characterized by albinism, mutations in LYST or RAB27A genes respectively)
In male infants, consider X-linked lymphoproliferative disease where natural killer cells are unable to kill Epstein-Barr virus.

So do ferritin (spectacularly high,eg >1000)! And repeat if initially normal! Other bloods as above. ESR surprisingly low, due to low fibrinogen cf underlying JIA. All inflammatory markers can be low if very ill due to consumption.

Specialist markers include CD25, CD163, IL-18, CXCL9.

Diagnostic criteria perform well in specific settings but none perfect – get an expert! And go looking for underlying causes if not already known to have. Genetic testing in particular can dramatically impact on diagnosis and management.

MRI Brain and lumbar puncture for infants, known genetic disorder, or clinical indications – do cytopathology.

Treatment

For probable cases with worsening organ dysfunction, consider immunomodulatory treatment while diagnostic resting still ongoing. Empirical treatment can be high dose steroids, Anakinra or IVIG, plus treatment of underlying infection/malignancy. [EULAR/ACR 2022 diagnostic criteria]

Beighton score

January 8, 2015General paediatrics, Rheumatologyadmin

Used for assessing hypermobility, in other words lax joints (“double jointed”).

1 for each side of passive dorsiflexion of 5th MCP to 90deg, opposition of thumb to volar aspect forearm, hyperextension of elbow/knee, and placing of hands flat on floor with straight knees.

4+ needed for hypermobility syndrome (for adults), other major criterion is arthralgia for 3+ months in 4+ joints. Minor criteria include:

1st degree relative,
recurrent dislocation,
3+ soft tissue lesions (eg bursitis, tenosynovitis),
abnormal skin (striae),
drooping eyelids,
varicose veins,
Marfanoid habitus
etc.

Other features of hypermobility syndrome in childhood include late walking, poor ball catching and handwriting, tiring easily.

Adults often get autonomic dysfunction eg orthostatic intolerance, functional bowel problems. Chronic pain syndrome and downward spiral in mobility often seen.

Ehlers Danlos syndrome has many proposed subtypes, some of which are pure hypermobility, but in others hypermobility may not be very obvious at all (just fingers!?). Some types have severe cardiac complications.

Scottishpaeds

General paediatrics with a Scottish flavour

Category Archives: Rheumatology

Ehlers-Danlos syndrome

Haemophagocytic syndromes

Treatment

Beighton score