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Familial Hypercholesterolaemia

Cardiology, General paediatrics

Usually LDL receptor gene mutations (on liver, for removing lipids from blood). One Apo-B mutation (on LDL) identified.  Least common is PCSK9 mutation – higher degradation of receptor, most severe.

If normal BMI, elevated LDL, autosomal dom inheritance, normal TFTs then 95% LDL receptor defect.

If one sibling has a LDL double that of another sibling, 99.8% LDL receptor mutation.

Highly heterogeneous in UK, over a 1000 mutations.

Estimated 1/500 in most countries [but in Denmark found 1/137, Holland has found 1 in 232].  So prob only 12% of cases identified in UK, even less in young individuals!

DNA screening cf lipid testing cost effective (and enhances cascade screening).  Using LDL only, 8-15% false neg and pos, due to overlapping of ranges.  Gene scoring (using SNPs) for mutation neg clinical cases helps to find polygenic cases. But 40% less risk of disease so cascade testing less effective.

American college of med genetics have recommended that familial hypercholesterolaemia (FH) mutations detected on whole genome should be reported to patient.

Cases of sudden cardiac death in 4-6yr olds reported in homozygous.  Heterozygous cases still important – 100X coronary risk age 20-40yrs…

Diagnosis

Diagnosis in childhood could save 50 healthy life years!!!  Dutch cascade screening since 1994 stopped last year. Only 1/3 of known paed cases came clinically, hence big gap in case finding.

Simon Broome criteria – (else use Dutch system) distinguishes Definite FH vs Possible.

  • Definite = DNA pos for known mutation, else tendon xanthomata (personal or 1st or 2nd deg relative) plus cholesterol as below.
  • Possible = cholesterol concentrations as below PLUS:
    • Family history of myocardial infarction: aged younger than 50 years in second-degree relative or aged younger than 60 years in first-degree relative.
    • Family history of raised total cholesterol: greater than 7.5 mmol/l in adult first- or second-degree relative or greater than 6.7 mmol/l in child, brother or sister aged younger than 16 years.

Cholesterol cut offs for Simon Broome

Total cholesterol LDL-C
Child/young person > 6.7 mmol/l > 4.0 mmol/l
Adults > 7.5 mmol/l > 4.9 mmol/l

Refer both definite and possible cases for DNA testing. Plus there are age/sex specific cholesterol cut offs for relative of a known case where DNA is negative.  NICE standard is that children with possible FH should be offered diagnostic tests by age 10.

Given how prevalent use of statins is now, it’s harder to get a positive family history! So history of grandparents more important! 10% have no family history

Only 4% of heterozygotes have xanthomas (can be in buttock cleft, but only look if found elsewhere!). Arcus at 6 oclock in children, all round in adults. Palpable in Achilles tendon rather than seen? Pain in achilles often reported! Resolve with treatment.

Management

NL guidelines – 5-7yr diet etc only.  Diet with plant sterols can drop LDL by 7%

Over 10yrs, treatment (high dose, low dose, combination) depends on mutation and LDL. Most experience with pravastatin.

LDL apheresis as treatment.

Excellent safety and tolerance of statins. Significant reduction within 2 years.

Like any regular medication, compare it to toothbrushing.  Do both at the same time!

Most cardiologists don’t consider FH when high cholesterol found. Nurses? Via labs?

Check growth, puberty, healthy lifestyle. Update family pedigree, contraception.

Smoking confers massive additional risk.  Albert Wiegman has had a 5yr old admitting to smoking…

Treating from age 6.

Outcome

10yr follow up submitted – mean age 24yrs. 7 already older than the age their parent had event. LDL still higher than sibs.

 

Boys have higher risk of cardiac death then girls, but smoking gives girls worse risk than boys.

Intima media thickness – increases year on year, so earlier treatment the better?  Even before age 8 significantly different from non FH.

 

In NICE audit, majority of children not on treatment, and being seen in adult lipid clinics.

No evidence that low fat diets etc are affecting growth (limited numbers so far).

Homozygous FH being recommended as rare disease, so deserving of national specialist service.

 

 

 

Peanut allergy

Allergy, General paediatrics

See also Prevention, pregnancy, EAT/LEAP studies and immunotherapy.

One of the most common food allergies, and a frequent cause of anaphylaxis.  Peanut is technically a legume, although there is cross-reactivity with tree nuts so often included when people talk about “nuts”.  Always consider if there are potentially other allergies to lentils, sesame, tree nuts eg cashew etc.

Also known as groundnut or monkey nut.

[Gary Stiefel, Leicester Royal, BSACI guideline peanut allergy]

Diagnosis

Wide range of potential peanut proteins.  In US study, vast majority were Ara h1/2 positive, but European more diverse. h1, h2, h3 most common for systemic reactions.  You would think testing with whole peanut would be more sensitive but component testing probably more sensitive and specific than total IgE – but not better than skin prick testing.

peanut allergy diagnosis BSACI 2017With a decent history, SPT >3mm or IgE >0.35 sufficient.

Before proceeding to a hospital challenge, footnote suggests either 2 negatives, or else both IgE and SPT negative.

Distinguish Pollen Food Syndrome – ie older, rhinitis, oral allergy symptoms with nuts/fruit. These kids will have a milder allergy.  Hazelnut mostly (Cor a1) but almond, walnut too. But can coexist with more severe allergy! Doing grass/birch pollen would support diagnosis, doing components might help assess prognosis. If history unclear, but positive IgE/Skin prick test then do components h2 and h8 (list of different cut offs for different commercial products given, with related specificity/sensitivity, just says positive/negative in flow chart). Footnote suggests adding Ara h 1, 3 and 9 as also suggest primary peanut allergy even if Ara h 2 neg.

Sibling risk 5-9%. Too low to justify routinely screening.  If family likely to just avoid forever, living in fear, then consider SPT to encourage home challenge!?

Prognosis

Up to 20% will outgrow, usually before age 8. Review may not be necessary if PFS only.  Follow up is essentially about education.  Testing can be done periodically, depending on resources.

In a study of adults coming to allergy clinics, 10% of peanut allergic turned out not to be.  Partly this would have been because the diagnosis was wrong (many had never actually reacted to peanut in the past).  Having eczema meant you were more likely to still be positive on testing.  Having asthma and being male made it half as likely you would not be allergic anymore.  But many of the cases described were not formally challenged so these results are of limited value.  [Poster at AAI 2021, Rima Rachid]

Avoidance

Difficult, as often used in biscuits, chocolate, ethnic foods eg satay.

As for any food allergy:

Peanut needs to be specified on food labels under UK/EU law.

Precautionary labels – impossible to eliminate risk. Often these “may contain” warnings and similar just say “nuts” without specifying whether the risk is from peanut or a tree nut (the company may be able to give further information if you enquire directly). 

Snack foods with precautionary labels are higher risk eg biscuits, cakes [Helen Brough].

Balance between convenience and risk (probably a very small risk, as many families ignore these warnings to some degree).  Stratify risk according to type of food, previous reactions, threshold, asthma, illness, time of day, location etc. Crossing the road metaphor – choose a safe place!

Should you avoid all nuts?  Some kids will be allergic to other (tree) nuts, but not all.  Andrew Clark reports v low rate of accidental reactions, 3%, with avoidance of all nuts. But increases quality of life to be allowed other nuts!  Risk assessment for each individual person!

Peanut oil

Probability of any reaction to refined peanut oil is remote (Blom et al, 2017). Little evidence that anyone has ever reacted to refined peanut oil. Code of practice is that presence of UNREFINED peanut oil should be declared on bottles of oil (UK and Europe).

But peanut oil, even if refined, still has to be declared on food labels.  Beware unrefined oil in ethnic foods.  Peanut oil also found in some medicines eg vitamins, antibiotic creams.

Some suspicion that peanut oil in cosmetics and pharmaceuticals might lead to sensitization and subsequent peanut allergy, even if not enough peanut protein to cause a reaction in an allergic person. So advice is avoid if you have a strong family history of allergy.

Immunotherapy

See Peanut immunotherapy.

X-linked lymphoproliferative syndrome (XLP)

General paediatrics, Immunology

(also known as , Duncan’s syndrome)

An immunodeficiency due (in 50% of cases) to SLAM associated protein (SAP) defect, specifically affecting the handling of EBV, affected boys are normal until they meet the virus. Following infection, they develop profound secondary immune deficiency affecting T and NK cell function and antibody responses. The following clinical patterns (not mutually exclusive) are described (and can be presenting features):

  • severe infectious mononucleosis
  • malignant B cell lymphoma (ie monoclonal proliferation)
  • Lymphoproliferation viz hepatosplenomegaly (ie polyclonal proliferation)
  • aplastic anemia
  • panhypogammaglobulinemia
  • haemophagocytic lymphohistiocytosis (HLH)
  • vasculitis

The prognosis is very poor with 75-85% mortality. Confirmation of the diagnosis involves demonstrating EB virus genome in lymphocytes by DNA hybridization, without antibody response to EB nuclear antigen (EBNA). The mothers of affected boys also have abnormal EB virus serology, with persisting very high titers against viral capsid antigen. Treatment is with Rituximab (anti CD20), although EBV receptor is CD21. If diagnosed in a sibling before they are infected by the virus, regular IVIG as passive immunization can be attempted though its efficacy is unproven.

Autosomal forms have been described.

OMIM entry

 

Severe Combined Immunodeficiency (SCID)

General paediatrics, Immunology

Mixed bag of diseases, with combined T and B cell deficits. “Severe” tends to mean severe lymphopenia and panhypogammaglobulinaemia with poor prognosis. Usually a bone marrow problem, with defective maturation of precursors – so depending on where the block is there may or may not be T cells, B cells, NK cells. A problem further down the line at the signalling stage will tend to mean immunoglobulin is produced, but not functional, esp since T cell regulation is needed too. So the clinical picture may be of a combined defect even if B cells and immunoglobulin are present. On the other hand, some defects are “leaky”, ie some precursors do manage to develop past the block by having reversion mutations causing somatic mosaicism. The other possible source of T cells if present is that they may be maternal (do FACS CD3 vs TCR to discriminate). To test, find appropriate T cell markers. Such T cells usually not functional but may ameliorate severity or prevent progression.

Typical presentation

Affected babies appear well at birth and are normally grown. Problems usually start within the first few months of life. Common presentations are:

  • Chronic diarrhoea and failure to thrive – often due to persistent and sometimes multiple gastrointestinal infection, +/-food intolerance.
  • Candidiasis
  • Severe bacterial infections esp pneumonia unresponsive to standard treatment
  • Atypical infections eg Pneumocystis jiroveci/carinii, disseminated BCG infection. PCP can be acute or chronic, causes interstitial pneumonia with disproportional hypoxia for degree of illness, LDH is often raised (non-specific, implies tissue invasion).
  • Reticular skin rash +/-mildly deranged LFTs – Graft-versus-host disease (GVHD) – since you can’t reject foreign tissues, you may show GVHD if maternal lymphocytes cross the placenta (usually mild) or via breast-feeding (very mild, not a contraindication). Role in gastrointestinal symptoms? More severe GVHD can follow blood transfusion – hence all lymphopenic patients should get irradiated blood to kill donor white cells. Differential is disseminated CMV, CD40 ligand deficiency, Omenns, ICF. Diagnosis is by finding 2 cell populations by chimerisms.
  • Occasionally SCID can present like Langerhans cell histiocytosis with dramatic erythrodermic or scaly rash, organomegaly (Omenns).

On examination (usually), no lymph nodes; no thymic shadow on chest X-ray (development of thymus requires appropriate signals from bone marrow). Hepatomegaly (?). Investigations usually reveal lymphopenia (<2.8 in first year), and there may or may not be NK cells – the exact pattern helps you work out where the block is. Odd results may reflect presence of maternal lymphocytes! Mitogen responses (proliferation studies) are usually absent. IgG will usually be present from Mum, but gets used up quickly! IgA and IgM may be present if B cells are present, but usually limited clonal diversity so not much function and no specific antibody responses.

Subtypes

B- NK- is ADA. B+ NK+ is IL7R defect. B+ NK- is gamma chain or JAK3 (the two bind to each other). B- NK+ is RAG or Artemis. Bare lymphocytes (T but not CD4) are HLA deficient.

Complex, because the defect can relate to cytokine signalling, T-cell receptor signalling, receptor gene recombination etc.

The biggest group are T- B+ NK-: the main cause is Gamma chain deficiency, which is X-linked. About 50% of all SCID. The Gamma chain is found in numerous cytokines (IL-2, 4, 7, 9 and 15), hence why it causes severe problems. JAK3 binds to gamma chain so causes an identical syndrome.

The next main group are T- B- NK-: Adenosine deaminase (ADA) deficiency is the main cause. Accumulation of toxic deoxyadenosine triphosphate (d-ATP) in lymphocytes leads to cell death. All cell lines are reduced. Additional features are:

  • Skeletal abnormalities (cupping deformities of the ends of the ribs, abnormalities of the transverse vertebral processes and the scapulae) are seen in up to 50% of cases and can be correlated with histological changes.
  • Neurodevelopmental problems may also occur in some patients.

Occasional cases of ADA deficiency have been described, where inexplicably, immune function is normal. The diagnosis is confirmed by assay of red cell ADA activity (Purine lab, Guy’s). First trimester antenatal diagnosis is possible. Gene therapy is done in London and Paris.

Purine nucleoside phosphorylase (PNP) deficiency is initially less severe than ADA deficiency but progresses with age. It is autosomal recessive (gene is on chromosome 9). The toxic metabolite is deoxyguanosine triphosphate. Immunoglobulin levels and antibody responses are initially normal but in the late stages levels fall.

PNP vs ADA

  • Onset of symptoms is usually later, can be delayed for several years.
  • Predominantly cell-mediated defect (viruses, fungi, GVHD).
  • Marked tendency to autoimmune disease, esp hemolytic anemia (even red cell aplasia).
  • No skeletal abnormalities, but more neurodevelopmental probs.
  • Partial, asymptomatic, forms of the deficiency have not been reported.

Reticular dysgenesis (autosomal recessive) is characterized by an absence of myeloid as well as lymphoid precursors, so no neutrophils or macrophages. Platelets and red cells are usually OK but can be low too! Even more severe than other forms of SCID, tends to present very early. Often GVHD rash. Hard to transplant…

The T- B- NK+ group are to do with VDJ recombination. The main one here is RAGs (recombination activating genes, 1 and 2) defect. If you can’t recombine these variable areas, then you can’t develop the necessary diversity in antigen receptors on T and B cells. Artemis and Ligase 4 similarly. NK don’t use them so they’re fine. Diagnose by looking at Ig gene rearrangements.

Ommen’s syndrome is a leaky B- SCID, usually a RAG defect, but characterised by:

  • infiltrative skin rash resembling seborrheic dermatitis (scaling, erythroderma): histologically, proliferation of CD8/CD4 double negative cells and histiocytes.
  • hepatomegaly and lymphadenopathy
  • lymphocytosis but with marked eosinophilia and raised IgE levels

Diagnosis is confirmed by showing limited TCR Vbeta clonal populations (the few clones leaking past the block expand in the periphery to cause the signs). Differential is GVHD (usually milder, not lymph nodes usually), congenital ichthyosis and Nethertons syndrome (autosomal recessive ichthyosis with immunodeficiency and growth failure). Interferon gamma may produce some clinical improvement but definitive treatment is with bone marrow transplantation.

The final group, T- B+ NK+, is a mixed bag of different problems, all to do with signal transduction:

  • ZAP-70 defect (CD8 deficiency, AR) – defective kinase, part of the CD3/TCR complex. Whereas CD8s are absent, CD4 and other cells are present.
  • JAK-3 defect – Janus kinase 3, a tyrosine kinase, interacts with the STAT (signal transduction and activators of transcription) family (AR).
  • IL7R defect

Defects in cytokine production are not really SCID:

  • IL-1, IL-2 and interferon gamma deficiency described, result in a spectrum of clinical problems including failure to thrive and opportunistic infections. Humoral immunity is relatively preserved.
  • Interferon gamma receptor defects predispose to disseminated atypical mycobacterial infection (see above).
  • IRAK (IL1R Associated Kinase) defect – like NEMO, broad range of cytokines affected. Typical infections are Pseudomonas, pneumococci, salmonella. NOT candida, viruses, mycobacteria, fungi. 50% die within first 3 years, thereafter survival improves markedly.The following have normal cell populations but abnormal surface molecules:
    • Bare lymphocyte syndrome (AR). You have T cells, but they don’t differentiate into CD4 and CD8 cells. Usually due to defective HLA expression. T and B cell numbers are normal! CD4 count is low in Class II and the CD8 count in Class I deficiency. Confirmation of the diagnosis depends on demonstration of the absence of the HLA antigens on the cells. Other weird features:
      • lymph nodes are palpable and the thymus is normal size (not histologically normal, mind you).
      • Mitogen responses are normal but antigen specific responses and delayed hypersensitivity tests are negative.
    • CD3 deficiency – also gives normal numbers of circulating T and B cells, so thymus and lymph nodes present. CD3 actually made up of several different chains, so In delta chain defect, the T cells make it to the thymus but don’t progress into the circulation.
    • Fas (CD95) deficiency = Autoimmune Lymphoproliferative Syndrome (30% have unknown mutations). This is a cell surface molecule important in apoptosis, hence lymphoproliferation ie massive lymphadenopathy, hepatosplenomegaly (but variable). It is expressed on thymocytes and activated T cells. Most obvious manifestation of autoimmunity is cytopenias. CD4 cells are low but lymphocyte count is normal by virtue of a proliferation of CD4/CD8 double negative cells (eg 30-60% of total). LNs have characteristic histology. Rx immunosuppression, usually pred and high dose IVIG are sufficient although may need extended treatment. MMF and rituximab have been used.
    • OKT4 deficiency is a defect in an epitope on the CD4 molecule recognized by a monoclonal antibody of that name. There is a mild immunodeficiency and a tendency to autoimmune disease.
    • Idiopathic CD4 lymphocytopenia. Usually adults, but can be seen in children. Affected individuals are highly susceptible to opportunistic infections, obviously; immunoglobulin levels and antibody responses are generally normal. The CD4 cell count seems to remain stable for a prolonged period cf HIV infection. Prophylaxis against Pneumocystis carinii infection should be given.

    Management of SCID

    Flow cubicle, sterile handling, Septrin, Itraconazole, IVIG prophylaxis. If unable to get flow, discharge from general paeds ward!

    PEG-ADA available for ADA deficiency. Use d-ATP levels to guide dosing. Treat while looking for transplant match.

    BMT or PBSC if match available. Haploidentical (ie parent) BMT have poor results in Europe but currently 80% success rates in UK (cf 97% success for full HLA match). No big breakthrough in BMT science, just incremental improvements in conditioning regimens, supportive care, graft manipulation. Non SCID success rate is currently 69%; the rate is actually falling as more risky cases are now taken on. MUD for Wiskot Aldrich has 85% 10yr survival rate; a good MUD, using genomic rather than serological matching, is probably just as good as a sibling transplant. Other issues:

    • Cord transplants: new cord bank in Newcastle. Better engraftment cf regular BMT but you still need a good match to avoid GVHD. Above 15kg, 1 cord is unlikely to yield enough cells – use 2?
    • If CMV infected, then using a CMV pos donor may be a good thing!
    • Busulphan usually makes you infertile.
    • Fludarabine/melphalan and Campath looks like a good conditioning regimen but historical controls of limited meaningfulness in BMT work. With lower intensity regimens, poor engraftment can always be boosted with more stem cells…
    • 20 CGDs done in Newcastle – 1 death after conditioning, 1 chronic GVHD else all successful!
    • Note strong age effect – older kids do worse. Psychological? More established organ damage?
    • Some “unnecessary” transplants may need to be done, to avoid missing an opportunity to cure 1 case that might go on to do badly in later life.
    • GVHD is rarely a long term problem in kids. Long term complications are infertility, hypothyroidism, prior organ damage.

    Gene therapy: T cell count starts to rise from 12 weeks onwards. GVHD may present at that point, but resolves spontaneously. 8 patients done so far in UK, only 1 non-responder who was an adult (not surprising, too old for thymic reconstitution), 2 have stopped IVIG treatment. More done in Paris, but 2 cases of malignancy; risk associated with number of cells returned. New gene therapy trials for CGD and ADA-type SCID.

Chediak-Higashi syndrome

General paediatrics, Immunology

A neutrophil disorder.

Issue is lysosomes, so large vesicles seen in neutrophils which have reduced function. Associated with albinism, developmental delay, bleeding disorder. The connection is that all have granules, and the defect is in way that endoplasmic reticulum sorts different products into different granules.

Griscelli syndrome is similar, associated with albinism but not developmental delay or bleeding. Can predispose to haemophagocytic syndrome. Differentiate from Chediak Higashi by light microscopy of hair (unevenly distributed large melanin granules cf evenly distributed; white under polarized light cf polychromatic).

Hermansky Pudlak II has the albinism, developmental delay and bleeding, but has pigmented macrophages instead of funny neutrophils. The neutrophil numbers as well as function are reduced, whereas other subtypes do not have any immunodeficiency. Check bleeding time.

Leucocyte adhesion disorders

General paediatrics, Immunology

3 types, 1= beta2 integrin defect (no adhesion), 2=selectin ligand (a fucose transporter; no rolling), 3= RAP1. Classically delayed cord separation (but actually seen in any neutrophil disorder), skin ulcers esp perianal, periodontitis, raised white cell count (because they are stimulated but don’t move about normally). Developmental delay and hepatosplenomegaly is seen in type 2, bleeding disorder seen in type 3.

Chemotaxis disorders tend to produce pretty mild disease eg periodontitis only…

Harmful parent child interactions

Child protection

Emotional abuse and neglect – There is an obligation on a Local Authority to prove their case. This is important both for allegations made against a parent and for assessing the capacity of a parent to look after the child. In some cases the allegations against a parent are unsubstantiated or not proven in any other context when that decision is taken by Social Work.

The Supreme Court decision In the matter of EV (A Child) (No 2) (Scotland) puts the emphasis on meeting the threshold test- a risk of serious detriment is not sufficient in itself. The Local Authority must prove its case. Crucially the Local Authority must address the three following issues through explanation and evidence:

  1. What is the detriment to the child in staying in the care of his or her parents?
  2. Why is this detriment considered serious?
  3. Why is this detriment considered likely?

Potentially more delays in system while evidence is gathered.

The message from the Supreme Court is clear that the onus is not on a parent to show they have the necessary parenting skills to parent the child, but rather for the Local Authority to assess and prove they do not have the capacity to parent the child.

Central serous chorioretinopathy

Allergy, General paediatrics, Surgical

Central serous chorioretinopathy (CSCR) = accumulation of subretinal fluid at the posterior pole of the fundus, ultimately leading to retinal detachment. Typically affects one eye only.  Vision becomes blurry and distorted, with objects often appearing smaller in the affected eye. May also cause difficulty with bright lights and contrast sensitivity.

Mechanism unknown, but associated with use of systemic corticosteroids, pregnancy, and Cushing’s syndrome.  Recently also been described after local corticosteroids including inhaled, intranasal, topical and periocular (!). Rare though.

Although blurred vision is a symptom of CSCR, it can be a side effect of periocular steroid treatment, as well as a symptom of whatever underlying eye condition is present (if any).

MHRA therefore says you should inform patients they should report any vision problems or disturbances.

[MHRA]

Webcam clinics

Patients,

Webcam clinics for diabetes (Newham, all ages) – mean duration only 9 minutes for both consultants and nurses, cf 25/30 minutes for face to face!  DNA rate 13% cf 28% for face to face.

Patients felt HCPs more focussed on them, other studies have confirmed that eye contact is better! But feels more impersonal, so prior relationship is important.

Trichotillomania

Clinical, General paediatrics, OPD

Or repetitive hair pulling.  Previously classified as an impulse control disorder, ie a sense of tension that is only “satisfied” when hair is pulled out. However, many children do not get this tension and gratification so in DSM-V trichotillomania is included among obsessive-compulsive and related disorders.

Dutch cohort mostly girls, literature says no gender difference!   Nail biting can co-exist, as can stereotypies.  Many kids will also eat their hair once it is pulled out.  Most common age of onset is in early adolescence (9-13 years), but frequently occurs in early childhood, even as early as 12 months of age.  Triggering factors identified include concerns about physical appearance, family and school issues, and concurrent illness.  Parents sometimes also pull their hair, so maybe (partly) learned.

Two distinct types of trichotillomania described: automatic and focused

  • Automatic – outside of own awareness, may not recall actual pulling, but may admit to ‘playing with their hair’ or may have been noted to pull their hair in a distracted state.  Children tend to fall into this category.
  • Focused – aware, in response to negative emotion or urges

Parents often miss the hair pulling and only present when hair clumps noticed on surfaces (esp bed –  presumably due to pulling in sleep) or bald patches appear.

On Examination

Exclamation mark hairs (thin proximally, at scalp, normal distally), usually thought of being evidence of alopecia areata, may be seen, so not very predictive.  Pull test – gentle traction on about 20 hairs in 3 different locations.  Positive if more than 5 hairs extracted – suggests active alopecia areata.  You may miss dormant alopecia, but in that case hair regrowth should occur.

[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4857813/]