Category Archives: Haem/Oncology

Atypical HUS

March 16, 2016General paediatrics, Genetics, Haem/Oncology, Renaladmin

Most Haemolytic Uraemic Syndrome is associated with a diarrhoeal illness (D+ HUS), esp E coli O157.

Atypical HUS is a bad name for HUS that develops in certain individuals due to a genetic, complement disorder. Disease is typically triggered by infection, esp respiratory tract, else diarrheal illness in 80% of pediatric forms.

Consider in young infants (less than 5% of D+HUS cases occur before the age of 6 mo), severe cases, non-colitis.

The penetrance of the disease among carriers of mutations in CFH, CFI and MCP genes is approximately 50%-60%.

Low C3 levels are a clue (seen with mutations in CFH, CFI and MCP). In almost all cases of aHUS C4 levels are normal. Normal C3 levels do not however exclude a mutation. Check factor H and factor I too.

Diagnosis

Measure CFH, CFI and MCP levels using radio-immune-diffusion assay (RIDA) or FACS. This however fails to detect low protein levels in 25%-75% of mutations, so genetic analysis also needed.

Check ADAMTS13 activity (as seen in thrombotic thrombocytopaenic Purpura, TTP) as part of differential.

Make sure you have enough blood samples before plasma exchange!

In neonates, screen for defective cobalamin metabolism (excess homocystine and methylmalonate in urine ). These babies have high mortality from multiorgan failure, a prompt diagnosis and B12 supplementation is their only hope.

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]

Lymphadenopathy

January 16, 2015Clinical, Common, General paediatrics, Haem/Oncology, Infectious diseaseadmin

A good proportion of healthy children will have palpable lymph nodes in the neck. Mostly these will be under 1cm in diameter. Acute enlargement as part of an upper respiratory tract infection is usually accompanied by tenderness, and affected nodes will reduce in size over 4-6 weeks.

Guidance from NICE and the Scottish Government provide criteria when children with lymphadenopathy should be urgently referred for suspected cancer.

These criteria include the following:

lymph nodes are non-tender and firm/hard
lymph nodes are greater than 2 cm in size
lymph nodes are progressively enlarging
other features of general ill-health, fever or weight loss
the axillary nodes are involved (in the absence of local infection or dermatitis)
the supraclavicular nodes are involved.

But caveat is “Always refer any patient with Repeat presentations (3 or more times) of any physical symptoms which do not appear to be resolving or following a normal pattern, taking into account parental and patient concern”.

No need to do bloods in the absence of any of these criteria. Not that cancer is the only concern – differential includes developmental lesions (branchial cysts etc), TB, Cat-scratch disease, non-tuberculous mycobacterial infection (esp in neck). These are always more than 2cm and there may also be systemic features and/or overlying skin discolouration too.

Malignancies often present in the head/neck region. Hodgkins lymphoma usually affects teenagers, Non-hodgkins tends to affect school age children, neuroblastoma tends to affect pre-school children. B-symptoms (recurrent fever, weight loss, night sweats, pruritus, lethargy) are only seen in a minority but does suggest more advanced disease, of course. Airway or voice changes, swallowing difficulty, Horner’s syndrome, superior vena cava syndrome may all be seen due to mass effect. Most neuroblastomas have an abdominal mass. Nasopharyngeal carcinomas are seen so look in the nose/throat.

Scottishpaeds

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