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Advanced Systemic Mastocytosis Treatment London | KIT D816V Testing

4th June 2026

London Allergy and Immunology Centre

Advanced Systemic Mastocytosis: Diagnosis, KIT D816V Testing and New Targeted Treatments

A specialist overview for patients and clinicians on advanced systemic mastocytosis, including C findings, molecular testing, avapritinib, midostaurin and emerging KIT D816V inhibitors such as bezuclastinib.

Important: This article is for education only and does not replace specialist medical advice. Advanced systemic mastocytosis is rare and should be assessed by clinicians experienced in mast cell disorders, haematology, allergy and clinical immunology.

What is advanced systemic mastocytosis?

Systemic mastocytosis is a clonal mast cell disease in which abnormal mast cells accumulate in organs such as the bone marrow, liver, spleen, gastrointestinal tract and bones. Most patients have non-advanced disease, but a smaller group develop advanced systemic mastocytosis, where mast cell infiltration causes measurable organ damage.

Aggressive SM

Systemic mastocytosis with organ damage caused by mast cell infiltration.

SM-AHN

Systemic mastocytosis with an associated haematological neoplasm; this is the most common advanced subtype.

Mast cell leukaemia

A rare and aggressive form with a high mast cell burden and usually rapid clinical progression.

advanced systemic mastocytosis showing abnormal mast cells, KIT D816V mutation, bone marrow involvement, gastrointestinal organs, blood testing and targeted treatment for mast cell disease.

Advanced systemic mastocytosis is defined by organ damage directly caused by mast cell infiltration. These are known as C findings. Examples include low blood counts, liver dysfunction with portal hypertension or ascites, enlarged spleen with hypersplenism, malabsorption with weight loss, and significant bone disease such as large osteolytic lesions or pathological fractures.

The key diagnostic concept: C findings

Symptoms alone are not enough

Flushing, abdominal discomfort, brain fog, bone pain, fatigue and anaphylaxis can occur in mast cell disorders, but advanced disease is diagnosed by objective organ damage, not by symptom severity alone.

KIT D816V: why molecular testing matters

Most adults with systemic mastocytosis carry the KIT D816V mutation, which drives abnormal mast cell growth and survival. Testing for KIT D816V helps confirm the diagnosis, assess disease burden and guide targeted treatment choices.

A standard next-generation sequencing panel may miss KIT D816V when the variant allele frequency is low. If clinical suspicion remains high, more sensitive techniques such as digital droplet PCR or allele-specific PCR may be needed, especially in patients with indolent or low-burden disease.

Current treatment options

Treatment	Main role	Important safety points
Midostaurin	Multi-kinase inhibitor used in advanced systemic mastocytosis.	Nausea, vomiting, diarrhoea and blood count suppression may occur.
Avapritinib	Potent targeted KIT D816V inhibitor with deep and durable responses in advanced SM.	May cause oedema, cognitive effects and risk of intracranial bleeding. It is not recommended with very low platelet counts.
Cladribine	Sometimes used when rapid cytoreduction is needed.	Can suppress immunity and blood counts; requires specialist monitoring.
Imatinib	Only useful in selected rare cases without KIT D816V or with imatinib-sensitive mutations.	Not effective for typical KIT D816V-positive systemic mastocytosis.

Bezuclastinib: an emerging KIT D816V inhibitor

Bezuclastinib is an investigational, next-generation KIT D816V inhibitor being studied in systemic mastocytosis. Its key mechanistic distinction is potent activity against mutant KIT D816V while aiming to spare wild-type KIT and related kinases.

Unlike avapritinib, bezuclastinib has been described in clinical development as having minimal brain penetration. This is clinically important because it may reduce concerns about cognitive adverse effects and intracranial bleeding risk. However, all targeted therapies can still have side effects and require careful specialist monitoring.

Corrected safety summary

Bezuclastinib should not be described as having a greater CNS risk than avapritinib. Current clinical development highlights its selectivity and minimal brain penetration as potential advantages. Its final place in treatment will depend on full peer-reviewed trial data, regulatory review and real-world safety experience.

Supportive care remains essential

Even when targeted treatment is used, patients with systemic mastocytosis usually need a personalised supportive care plan. This may include trigger avoidance, emergency medication, assessment of anaphylaxis risk, bone density monitoring, vitamin D optimisation, osteoporosis treatment when indicated, and review of gastrointestinal symptoms, nutrition and weight loss.

When to seek specialist review

Unexplained anaphylaxis, persistently high tryptase, abnormal blood counts, enlarged liver or spleen, unexplained weight loss, fractures, osteoporosis or suspected KIT D816V-positive disease should prompt specialist assessment.

What a specialist clinic may arrange

Assessment may include serum tryptase, blood tests, KIT D816V testing, bone density scan, allergy and anaphylaxis review, haematology input, bone marrow assessment and personalised treatment planning.

Practical action points for patients

Ask whether your disease is non-advanced or advanced systemic mastocytosis.
Confirm whether KIT D816V has been tested using a sufficiently sensitive method.
Carry adrenaline auto-injectors if prescribed and ensure you know when and how to use them.
Discuss bone density monitoring, calcium and vitamin D status, and osteoporosis prevention.
Before avapritinib, platelet count and bleeding risk must be carefully reviewed by the treating specialist.
Consider review in a centre with experience in mast cell disorders when the diagnosis or treatment plan is uncertain.

Specialist allergy and immunology assessment in London

London Allergy and Immunology Centre provides specialist assessment for mast cell activation symptoms, recurrent anaphylaxis, raised tryptase and suspected mast cell disorders. Patients with suspected advanced systemic mastocytosis may require coordinated care with haematology and specialist mastocytosis services.

Appointments: Please contact the clinic to arrange a specialist consultation and review of previous test results.

References and further reading

World Health Organization and international consensus classifications of systemic mastocytosis and advanced systemic mastocytosis.
Valent P, Akin C, Hartmann K, et al. Updated diagnostic criteria and classification of mast cell disorders.
DeAngelo DJ, Radia DH, George TI, et al. Avapritinib in advanced systemic mastocytosis: EXPLORER and PATHFINDER clinical trial data.
Gotlib J, Kluin-Nelemans HC, George TI, et al. Midostaurin in advanced systemic mastocytosis.
Cogent Biosciences. Bezuclastinib APEX study updates in advanced systemic mastocytosis.
American Academy of Allergy, Asthma and Immunology. Mastocytosis patient information and clinical resources.

Early SLIT Immunotherapy for Hay Fever and Asthma Prevention London

13th May 2026

SLIT Immunotherapy London

Early SLIT Immunotherapy: Could Treating Hay Fever Earlier Help Protect Against Asthma?

New medical evidence suggests that sublingual allergen immunotherapy (SLIT) may be more than symptom control. For carefully selected patients, it may help change the long-term course of allergic rhinitis and allergic asthma.

Key message

SLIT immunotherapy is increasingly being viewed as a disease-modifying treatment for allergic rhinitis and allergic asthma, rather than only a final option when antihistamines and nasal sprays are not enough.

What is SLIT immunotherapy?

Sublingual allergen immunotherapy (SLIT) is a specialist allergy treatment designed to gradually train the immune system to tolerate a specific allergen. It may be used for selected patients with allergic rhinitis, allergic conjunctivitis and allergic asthma caused by triggers such as grass pollen, tree pollen, house dust mite or animal dander.

Unlike standard medicines, which mainly reduce symptoms while they are being taken, SLIT aims to reduce the body’s allergic response over time. Treatment is usually administered as liquid allergen drops under the tongue according to the prescribed treatment plan.

How SLIT works

Small amounts of allergen are introduced regularly under the tongue to encourage immune tolerance over time. The treatment plan is individualised according to the allergen profile, symptoms and medical history.

Why is earlier treatment being discussed?

A 2026 expert review in Current Opinion in Allergy and Clinical Immunology highlights a shift in thinking. Traditionally, allergen immunotherapy was often considered only after symptoms remained troublesome despite medication. However, newer real-world evidence suggests that starting immunotherapy earlier in suitable patients may offer a “window of opportunity” to influence the natural history of allergic airway disease.

This is particularly relevant for patients with persistent allergic rhinitis, with or without mild to moderate allergic asthma. Allergic rhinitis and asthma are closely linked, and untreated or poorly controlled nasal allergy may contribute to lower airway symptoms in some patients.

Potential benefits of earlier SLIT immunotherapy

Reduced need for long-term allergy medication
Improved control of allergic rhinitis symptoms
Fewer severe asthma exacerbations in some patient groups
Possible reduction in the risk of developing asthma
Possible reduction in the development of new allergen sensitisation
Long-lasting benefit after completion of treatment in selected patients

What does recent evidence show?

Large real-world studies, including the REACT programme and the EfficAPSI study, suggest that adding allergen immunotherapy to standard care may reduce medication use, severe asthma exacerbations and healthcare use over long-term follow-up.

The 2026 review also highlights that younger patients may gain particular benefit when treatment is started before allergic airway disease becomes more established. This supports the idea that allergic rhinitis should not always be viewed as a minor condition, especially when symptoms are persistent, seasonal year after year, or associated with wheeze, cough or exercise-related breathing symptoms.

Who may be suitable for SLIT immunotherapy?

SLIT is not suitable for everyone. It should only be considered after specialist allergy assessment, including a careful clinical history and confirmation that symptoms match relevant IgE sensitisation on skin prick testing or blood testing.

You may be considered if you have:

Moderate to severe hay fever
Persistent house dust mite allergy
Allergic rhinitis with confirmed pollen, mite or animal allergy
Symptoms despite regular antihistamines or nasal sprays
Allergic asthma that is mild to moderate and controlled enough for treatment

A specialist review is essential if you have:

Uncontrolled asthma
A history of severe allergic reactions
Multiple allergies requiring prioritisation
Other medical conditions or regular medication
Uncertainty about the main allergen causing symptoms

Why accurate diagnosis matters

The success of SLIT depends on selecting the correct allergen. For example, a patient with spring symptoms may be reacting to birch pollen, grass pollen, plane tree pollen, or more than one pollen. A patient with year-round symptoms may have house dust mite allergy, animal dander allergy, mould allergy, non-allergic rhinitis, or a combination of causes.

At a consultant-led allergy clinic, testing may include skin prick testing, specific IgE blood testing and, where appropriate, molecular allergy testing. This helps confirm whether immunotherapy is likely to be clinically relevant and which allergen should be prioritised.

Early treatment does not mean rushed treatment

Earlier SLIT means considering disease-modifying treatment before allergic disease progresses further. It does not mean starting treatment without proper assessment. The allergen profile, safety considerations and asthma control must all be reviewed carefully.

How long does treatment take?

SLIT immunotherapy is usually a long-term commitment. Many treatment courses continue for around three years, depending on the allergen and clinical response. The aim is to achieve sustained immune tolerance and longer-lasting benefit, rather than short-term symptom relief only.

Can SLIT replace antihistamines and nasal sprays?

Not immediately. Symptomatic treatment remains important, especially during the early stages of immunotherapy and during high pollen exposure. Many patients continue to use nasal sprays, antihistamines or eye drops as needed. Over time, some patients may need less medication, but this should be reviewed individually.

Why choose a specialist allergy clinic?

SLIT should be prescribed and monitored by clinicians experienced in allergy diagnosis, asthma assessment and immunotherapy safety. A specialist clinic can help identify the most relevant allergen, assess asthma risk and monitor response throughout the course.

Considering SLIT immunotherapy for hay fever, dust mite allergy or allergic asthma?

A consultant-led allergy assessment can help determine whether SLIT immunotherapy is appropriate for you or your child.

Book an Allergy Consultation

Summary

SLIT immunotherapy is increasingly recognised as a treatment that may modify the course of allergic respiratory disease. For suitable patients with confirmed allergic rhinitis, and especially those at risk of asthma progression, earlier discussion of immunotherapy may be clinically valuable.

The decision should always be personalised. The most important first step is accurate diagnosis, followed by careful selection of the correct allergen treatment plan.

Medical disclaimer: This article is for general information only and does not replace medical advice. Immunotherapy should only be started after assessment by an appropriately qualified allergy specialist.

References include: Lombardi C. et al. Allergen-specific immunotherapy at earlier stages of allergic respiratory diseases. Current Opinion in Allergy and Clinical Immunology. 2026; ARIA-EAACI allergic rhinitis guidance; AAAAI, London Allergy and Immunology Centre’s patient information on allergy immunotherapy.

Urticaria Allergic rhinitis Mental health

9th April 2026

ACARE & UCARE Accredited Centre

Mind, Mucosa and Skin

How chronic urticaria, allergic rhinitis and psychological wellbeing can affect one another

At the London Allergy and Immunology Centre, we take a whole-person view of allergy care. New research highlights that chronic spontaneous urticaria, nasal allergy symptoms and emotional wellbeing are often closely connected. This matters because better understanding of this link can help patients access more complete and effective care.

The link between chronic urticaria hives, allergic rhinitis symptoms and psychological stress in allergy patients

The connection between chronic urticaria, allergic rhinitis and psychological stress affecting overall wellbeing.

Quick overview

What this means
What is CSU?
What the study found
Rhinitis link
Stress and skin
How we help

Why this matters for patients with allergy and urticaria

Chronic spontaneous urticaria, often called CSU, is more than a skin rash. It can disrupt sleep, affect confidence, interfere with work and family life, and create constant uncertainty because symptoms may flare without warning. When allergic rhinitis is also present, the burden can become even greater. Nasal blockage, sneezing, poor sleep and persistent irritation may add to fatigue and emotional strain.

A 2026 study explored this triad of mind, mucosa and skin and showed that psychiatric comorbidities were very common among adults with antihistamine-refractory CSU receiving omalizumab. The findings support a more integrated model of care in which allergy, skin symptoms, sleep and mental wellbeing are considered together rather than separately.

What is chronic spontaneous urticaria?

Urticaria is characterised by itchy raised wheals, angioedema, or both. When symptoms persist for more than 6 weeks, the condition is defined as chronic urticaria. If the rash and swelling occur without a clear external trigger, it is called chronic spontaneous urticaria.

Many patients improve with antihistamines, but some continue to have frequent symptoms despite treatment. In these more difficult cases, specialist assessment is important to confirm the diagnosis, identify associated conditions, assess disease activity properly and consider advanced treatment options such as omalizumab where appropriate.

Common features of CSU

– Recurrent itchy wheals
– Swelling of the lips, eyelids, hands or other areas
– Symptoms lasting longer than 6 weeks
– Unpredictable flare-ups
– Sleep disturbance and reduced quality of life

What did the 2026 study find?

The study reviewed 72 adults with antihistamine-refractory CSU who received omalizumab and had a formal psychiatric evaluation at a tertiary allergy centre between 2015 and 2025. Most participants were female, with a median age of 45 years. Psychiatric diagnoses were identified in 90.3% of the cohort who underwent psychiatric assessment.

The most frequent psychiatric diagnostic group was anxiety disorders, followed by mood disorders and sleep-wake disorders. Generalised anxiety disorder was the single most common diagnosis. The authors also reported that allergic rhinitis was present in more than half of the cohort, suggesting an important upper-airway allergic burden in this patient group.

Study finding	Result
Patients included	72 adults with antihistamine-refractory CSU treated with omalizumab
Female participants	70.8%
Median age	45 years
Any psychiatric comorbidity	90.3%
Most common psychiatric group	Anxiety disorders
Allergic rhinitis in the cohort	51.4%

Why allergic rhinitis may worsen the overall burden

Allergic rhinitis is sometimes seen as a minor condition, but persistent nasal symptoms can have a major effect on quality of life. Blocked nose, sneezing, post-nasal drip, poor sleep and daytime fatigue may all contribute to irritability, reduced concentration and lower resilience. In patients who also have chronic urticaria, this can intensify the sense of being unwell.

The authors of the study suggested that allergic rhinitis may reinforce the psychodermatological loop by adding sleep disruption and chronic upper-airway inflammation to an already stressful skin condition. This is one reason why it is important for specialist clinics to assess the whole allergic picture rather than looking at hives in isolation.

When urticaria and rhinitis coexist, patients may experience

– More sleep disturbance
– Greater tiredness during the day
– Higher stress levels
– Lower quality of life
– A stronger perception that symptoms are difficult to control

The stress-skin connection in chronic urticaria

Patients often tell us that stress seems to aggravate their hives. This fits with what clinicians and researchers have observed for many years. Chronic urticaria can itself be stressful because flare-ups are unpredictable and visible. At the same time, stress may influence inflammatory pathways, itch perception and symptom severity, which can then further increase anxiety and distress. This creates a self-perpetuating cycle.

The 2026 paper describes this as a close interaction between psyche and skin. Biological pathways thought to be involved include stress-related neuroimmune signalling and mast cell-mediated inflammation. For patients, the important message is simple: the symptoms are real, the burden is real, and both the physical and emotional impact deserve proper attention.

This does not mean urticaria is “just stress”. Rather, it means stress, sleep problems, allergy symptoms and inflammation may all affect one another. That is why good management often requires more than a prescription alone.

Response to treatment in the study

Under omalizumab treatment, disease control improved significantly in this cohort. Median UAS7 scores fell from 42 before treatment to 7 at 24 months, while UCT scores rose from 0 to 14. These results support the role of specialist treatment in patients whose symptoms remain poorly controlled on antihistamines alone.

The authors also noted that improving urticaria control may bring psychological benefits and better emotional wellbeing. In practice, this reinforces the importance of identifying uncontrolled disease early and ensuring that patients receive an expert review rather than simply repeating ineffective treatment.

What this means for care at our ACARE and UCARE accredited centre

As an ACARE and UCARE accredited centre, we believe patients with chronic urticaria deserve expert, evidence-based and compassionate care. This includes careful diagnosis, assessment of angioedema and inducible triggers, review of coexisting allergic diseases such as allergic rhinitis and asthma, and evaluation of how symptoms are affecting sleep, mood and daily functioning.

Where appropriate, management may involve optimisation of antihistamines, consideration of advanced treatment pathways, investigation of associated conditions and practical support around trigger awareness, sleep hygiene and stress reduction. In some cases, collaboration with other professionals may be helpful so that care is truly patient-centred and holistic.

For patients, the key message is that severe hives and swelling are not only skin symptoms. They can affect confidence, sleep, relationships and quality of life. Recognising that full burden is an important step towards better outcomes.

When to seek specialist urticaria assessment

– Your hives or swelling have lasted longer than 6 weeks
– Symptoms keep returning despite antihistamines
– You have troublesome angioedema
– Sleep is regularly disturbed by itch or nasal symptoms
– You feel that stress, anxiety or low mood are making symptoms harder to manage
– You may have both urticaria and allergic rhinitis

Book an expert review

If you are living with chronic hives, angioedema or allergic rhinitis, our specialist team can help assess the full picture and create a personalised plan. We offer consultant-led allergy care with a focus on accurate diagnosis, better symptom control and improved quality of life.

Book an appointment

Reference

This article is based on the 2026 paper by Zeynep Yegin Katran, İsmet Bulut, Andaç Salman, Ali Baz, Galip Muzaffer Kürşat Küçükali and Özge Argın, which examined the relationship between chronic spontaneous urticaria, allergic rhinitis and psychiatric comorbidities in omalizumab-treated adults.

Please note that this blog is for general education and does not replace personalised medical advice. Diagnosis and treatment should always be based on an individual clinical assessment.

baked-milk-oral-immunotherapy-cows-milk-allergy

8th February 2026

Baked Milk Oral Immunotherapy: A New Advance in Cow’s Milk Allergy Treatment

Cow’s milk allergy (CMA) is one of the most common food allergies in children and can have a significant impact on daily life, nutrition, and family wellbeing. Strict milk avoidance is challenging, as milk proteins are present in many everyday foods, particularly baked products.A randomised clinical trial published in January 2025 has provided encouraging evidence that baked milk oral immunotherapy (BMOIT) may offer a safer and effective treatment option for selected patients with cow’s milk allergy.

At London Allergy and Immunology Centre, we closely monitor emerging research to ensure our patients benefit from the most up-to-date, evidence-based allergy care.

What Is Baked Milk Oral Immunotherapy (BMOIT)?

Oral immunotherapy (OIT) is a treatment approach designed to desensitise the immune system by exposing patients to very small, gradually increasing amounts of an allergen under specialist supervision.

Baked milk oral immunotherapy for cow’s milk allergy: a UK doctor consulting a mother and child, child drinking baked milk, immune system changes with IgE and IgG4 antibodies, desensitisation from baked milk to fresh milk, London landmarks in the background, and icons for safety, improved quality of life, and research insights

Baked milk oral immunotherapy (BMOIT) helps children with cow’s milk allergy build tolerance safely, guided by a UK allergy consultant, with immune system changes and improved quality of life

Baked milk OIT differs from traditional milk OIT because it uses milk that has been extensively heated, such as milk baked into muffins or cakes. Heating changes the structure of milk proteins, making them less allergenic while still capable of training the immune system to tolerate milk.

Many children with cow’s milk allergy can already tolerate baked milk, even if they react to fresh milk. This makes baked milk an attractive starting point for immunotherapy.

Key Findings From the January 2025 Study

The study, titled “Clinical and immunological outcomes after randomized trial of baked milk oral immunotherapy for milk allergy”, followed children aged 3 to 18 years with confirmed cow’s milk allergy.

Baked milk OIT was well tolerated, with most reactions being mild
70% of participants achieved desensitisation to baked milk
37% also developed tolerance to unheated (fresh) milk
No severe allergic reactions were reported during treatment

These findings suggest that baked milk oral immunotherapy may safely increase milk tolerance while reducing the risks often associated with traditional milk OIT.

How Does Baked Milk OIT Affect the Immune System?

In addition to clinical outcomes, researchers analysed immune markers to understand how tolerance develops during baked milk OIT.

Reduction in milk-specific IgE antibodies, which trigger allergic reactions
Increase in IgG4 antibodies, associated with immune tolerance
Favourable changes in immune cells involved in regulating allergic inflammation

These immunological changes confirm that baked milk OIT actively modifies the allergic immune response rather than simply masking symptoms.

Why This Research Matters for Families

Living with cow’s milk allergy can lead to anxiety about accidental exposure, nutritional concerns, and social challenges at school, childcare, and family events.

Baked milk oral immunotherapy may help by:

Increasing safety margins against accidental milk exposure
Expanding dietary options
Improving quality of life for children and their families

While not every patient is suitable for oral immunotherapy, this approach offers new hope for carefully selected individuals.

Is Baked Milk Oral Immunotherapy Available?

Baked milk oral immunotherapy should only be performed under specialist medical supervision. It is not suitable for all patients with cow’s milk allergy and requires careful assessment, monitoring, and long-term follow-up.

At London Allergy and Immunology Centre, we assess each patient individually to determine whether oral immunotherapy, including baked milk protocols, is appropriate and safe.

Expert Care at London Allergy and Immunology Centre

We specialise in the diagnosis and management of food allergies, including cow’s milk allergy, using the latest diagnostic tools and evidence-based treatments.

Comprehensive allergy assessments
Supervised food challenges
Personalised allergy management plans
Expert advice on emerging treatments such as oral immunotherapy

If your child has a cow’s milk allergy and you would like to explore current or future treatment options, our specialist team is here to help.

To book a consultation, please contact London Allergy and Immunology Centre.

This article is for educational purposes only and does not replace individual medical advice.