Clinical Immunology & Allergy Specialised Services

Category 316

Specialised Immunology

Primary immunodeficiency, complement disorders, autoinflammatory syndromes, hereditary angioedema

Category 317

Specialised Allergy

Severe/complex allergy, anaphylaxis, mastocytosis, brittle asthma, eosinophilic disorders, drug allergy

Multidisciplinary

Expert Team

Allergy, immunology, dermatology, ENT, paediatrics — working collaboratively for complex cases

Recurrent, severe, or unusual infections suggesting an underlying immune system problem

Life-threatening anaphylaxis with no identifiable trigger, or anaphylaxis despite avoidance

Recurrent angioedema without urticaria, particularly involving the throat, abdomen, or face

Episodic fever, rash, joint pain, or abdominal pain with no clear infective or autoimmune cause

Severe asthma, eczema, or urticaria unresponsive to standard treatments

Suspected mastocytosis, elevated tryptase, or an unexplained mast-cell disorder

Common Variable Immunodeficiency (CVID)

The most common symptomatic primary antibody deficiency in adults. Characterised by markedly reduced IgG (and usually IgA and/or IgM) with impaired antibody responses to vaccines. Presents with recurrent sinopulmonary infections, bronchiectasis, and increased risk of autoimmune complications. Treated with immunoglobulin replacement therapy (IVIg or SCIg).

X-linked Agammaglobulinaemia (XLA)

A severe B-cell deficiency caused by BTK gene mutations. Almost exclusively affects males. Presents with very low or absent all immunoglobulin classes and near-absence of circulating B cells. Severe recurrent bacterial infections from infancy. Requires lifelong immunoglobulin replacement.

IgG Subclass Deficiency & Specific Antibody Deficiency

Reduced levels of one or more IgG subclasses (IgG1–4) with impaired specific antibody responses to polysaccharide or protein antigens. May underlie recurrent respiratory infections despite normal total IgG. Diagnosis confirmed by pre- and post-vaccination antibody responses.

IgA Deficiency

The most common primary antibody deficiency, affecting approximately 1 in 500 people. Many patients are asymptomatic; others have recurrent respiratory or gastrointestinal infections. Also associated with autoimmune conditions and coeliac disease. Risk of severe transfusion reactions with blood products containing IgA — important surgical consideration.

Hyper IgE Syndrome & Hyper IgM Syndromes

Hyper IgE syndrome: very high IgE, recurrent staphylococcal skin infections and pneumonias, eczema, and skeletal abnormalities. Hyper IgM syndromes: normal or elevated IgM with profoundly reduced IgG, IgA, and IgE, leading to recurrent bacterial and opportunistic infections. Both require specialist molecular diagnosis and management.

Severe Combined Immunodeficiency (SCID)

Life-threatening absence of T and B cell function from birth. Requires urgent haematopoietic stem cell transplantation. Neonatal screening now identifies most cases in the UK.

Wiskott–Aldrich Syndrome

X-linked; triad of eczema, thrombocytopenia, and combined immunodeficiency. Increased susceptibility to infections, autoimmunity, and lymphoid malignancy. WAS gene mutations.

Ataxia Telangiectasia

ATM gene mutations causing progressive cerebellar ataxia, oculocutaneous telangiectases, combined immunodeficiency, increased cancer susceptibility, and radiation sensitivity. IgA deficiency common.

DiGeorge Syndrome (22q11.2 deletion)

Thymic hypoplasia resulting in T-cell lymphopenia; often with cardiac defects, hypocalcaemia, and facial dysmorphism. Severity of immune deficiency varies widely — most patients have partial rather than complete DiGeorge.

Chronic Mucocutaneous Candidiasis (CMC)

Persistent or recurrent Candida infections of the skin, nails, and mucous membranes due to specific defects in anti-fungal T-cell immunity. Associated with autoimmune polyendocrinopathy in some forms (APECED).

IFN/IL-12 Pathway Deficiencies

Mendelian susceptibility to mycobacterial disease (MSMD). Unusually severe infections with non-tuberculous mycobacteria or BCG vaccine. Caused by mutations in IFN-γ, IFN-γR, IL-12, IL-12R, STAT1, or related genes.

Chronic Granulomatous Disease (CGD)

Defect in the NADPH oxidase complex preventing neutrophils from generating the oxidative burst required to kill catalase-positive organisms (Staphylococcus, Aspergillus, Klebsiella). Presents with life-threatening pneumonias, abscesses, and granulomatous complications. Managed with long-term prophylactic antibiotics and antifungals; curative bone marrow transplant in selected cases.

Other Neutrophil Disorders

Leukocyte adhesion deficiency (LAD), Chediak–Higashi syndrome, severe congenital neutropenia (Kostmann syndrome), and cyclic neutropenia. All present with recurrent severe bacterial or fungal infections and require specialist molecular diagnosis.

Hereditary Angioedema (HAE) — Types 1, 2 & 3

HAE is caused by deficiency (Type 1, ∼85% of cases) or dysfunction (Type 2) of C1 esterase inhibitor (C1-INH), resulting in recurrent bradykinin-mediated attacks of subcutaneous and submucosal swelling. Laryngeal attacks carry a risk of fatal asphyxiation. Attacks do not respond to antihistamines or adrenaline — specific HAE treatments are essential.

Current UK treatments (2024–2025):

• On-demand: C1-INH concentrate (Berinert, Cinryze), icatibant (Firazyr)
• Long-term prophylaxis: Lanadelumab (Takhzyro), berotralstat (Orladeyo), C1-INH IV (Cinryze)
• Short-term pre-procedure prophylaxis: C1-INH IV

Full HAE information →

Complement Component Deficiencies

Deficiencies of early complement components (C1q, C1r/s, C2, C4) are associated with systemic lupus erythematosus (SLE)-like disease and recurrent bacterial infections. Terminal complement deficiencies (C5–C9) confer specific susceptibility to Neisseria infections (meningococcal and gonococcal disease) and require lifelong antibiotic prophylaxis and specific meningococcal vaccination. Properdin deficiency also greatly increases meningococcal risk.

Familial Mediterranean Fever (FMF)

Most common hereditary periodic fever syndrome. MEFV gene mutations (autosomal recessive). Recurrent episodes of fever with peritonitis, pleuritis, or arthritis lasting 1–3 days. Risk of AA amyloidosis if untreated. Colchicine is first-line treatment; IL-1 antagonists for colchicine-refractory cases.

TRAPS (TNF Receptor-Associated Periodic Syndrome)

TNFRSF1A gene mutations. Prolonged febrile attacks (typically 1–3 weeks) with periorbital oedema, migratory myalgia and rash, serositis. Autosomal dominant. Etanercept and IL-1 inhibitors (anakinra, canakinumab) are effective.

Cryopyrin-Associated Periodic Syndromes (CAPS)

NLRP3 gene mutations causing a spectrum from mild (Familial Cold Autoinflammatory Syndrome — urticaria-like rash triggered by cold exposure) through intermediate (Muckle–Wells Syndrome — plus sensorineural deafness and amyloidosis) to severe (NOMID/CINCA — chronic neonatal inflammation with CNS involvement). All respond dramatically to IL-1 blockade (anakinra, canakinumab, rilonacept).

Hyper IgD Syndrome (HIDS) / MVK Deficiency

MVK gene mutations (autosomal recessive). Recurrent febrile attacks every 4–6 weeks with lymphadenopathy, abdominal pain, diarrhoea, rash, and arthritis from infancy. Elevated IgD and IgA. IL-1 inhibitors and canakinumab are effective.

Other Syndromes

PAPA syndrome (Pyogenic Sterile Arthritis, Pyoderma Gangrenosum & Acne — PSTPIP1 mutations); Blau syndrome / early-onset sarcoidosis (NOD2 mutations — granulomatous arthritis, uveitis, dermatitis); IL-1 Receptor Antagonist Deficiency (DIRA — severe neonatal pustulosis and osteitis).

Severe & Recurrent Anaphylaxis

Life-threatening anaphylaxis with no identifiable trigger (idiopathic anaphylaxis), anaphylaxis despite confirmed allergen avoidance, or anaphylaxis associated with elevated tryptase suggesting underlying mast-cell disease. Requires comprehensive investigation including baseline tryptase, mast-cell markers, bone marrow assessment, and multidisciplinary management.

Mastocytosis & Mast-Cell Activation Disorders

Mastocytosis is a clonal mast-cell disease characterised by accumulation of neoplastic mast cells in skin (urticaria pigmentosa) and/or internal organs (systemic mastocytosis). Elevated baseline serum tryptase is the key marker. Systemic mastocytosis may be indolent or aggressive. Management involves trigger avoidance, antihistamines, and — in eligible patients — midostaurin (KIT D816V inhibitor) or investigational agents. Critically relevant to venom immunotherapy planning.

Multiple or Severe Food Allergy

Patients with multiple coexisting food allergies causing nutritional compromise, frequent severe reactions, or significantly impaired quality of life; those unsuitable for standard management; patients being assessed or treated with oral immunotherapy (Palforzia® for peanut) or other food OIT protocols under specialist supervision.

Bee & Wasp Venom Allergy

Grade III–IV systemic reactions to Hymenoptera stings, particularly in patients with elevated tryptase, mastocytosis, or multiple sting reaction risk factors. Venom immunotherapy (VIT) including conventional, rush, and ultra-rush protocols. Omalizumab co-therapy for patients who react to VIT.

Full venom allergy service →

Latex Allergy with Anaphylaxis

Severe IgE-mediated latex allergy causing anaphylaxis — particularly relevant for healthcare workers, patients with spina bifida (with high prevalence of latex sensitisation), and those requiring repeated surgical procedures. Multidisciplinary planning with surgical and anaesthetic teams. Latex avoidance protocols and, in eligible patients, latex allergen-specific IgE component testing (Hev b 1–11).

Brittle Asthma

Type 1 (persistent, chaotic variability in peak flow despite maximal therapy) and Type 2 (sudden severe attacks without warning in otherwise well-controlled asthma). Requires advanced lung function assessment, trigger identification, multidisciplinary management, and consideration of biologic therapies including omalizumab, mepolizumab, benralizumab, or tezepelumab.

Severe Eczema / Atopic Dermatitis

Widespread or recalcitrant atopic dermatitis unresponsive to topical corticosteroids, tacrolimus, and bandaging; patients considered for systemic therapy including dupilumab (Dupixent®), tralokinumab (Adtralza®), lebrikizumab, ciclosporin, or methotrexate. Shared care with dermatology consultants.

Severe Respiratory Allergy

Allergic rhinitis with complications (e.g. polypoid sinusitis, Eustachian tube dysfunction), occupational respiratory allergy, or severe rhinitis significantly impairing daily life or sleep quality, uncontrolled on maximal intranasal therapy. Allergen immunotherapy (SCIT/SLIT) or biologic therapy assessment.

Severe Chronic Urticaria & Angioedema

Chronic spontaneous urticaria (CSU) or angioedema refractory to high-dose antihistamines (up to 4× licensed dose). Assessment for omalizumab (Xolair®), dupilumab (FDA-approved for CSU 2025), and remibrutinib (BTK inhibitor 2025). Histamine release testing, autoimmune workup, and C1 inhibitor assessment to classify and direct therapy.

Urticaria & angioedema service →

Drug Allergy Assessment & De-labelling

Formal assessment of suspected reactions to penicillin, other antibiotics, NSAIDs, local and general anaesthetics, biologics, and other drugs. Skin testing, specific IgE, and supervised graded challenge. Formal de-labelling for up to 90% of patients labelled “penicillin allergic” who are not genuinely allergic — reducing antimicrobial resistance and improving care outcomes.

Drug allergy challenge service →

Vaccine Allergy Evaluation & Graded Challenge

Assessment of patients with previous reactions to vaccines (MMR, influenza, COVID-19, yellow fever, hepatitis vaccines) who require revaccination. Component testing, risk stratification, and supervised graded vaccination protocol in clinic with resuscitation facilities. Particularly important for travel health and occupational vaccination requirements.

Desensitisation & Immunotherapy

Drug desensitisation protocols for patients who require a drug they are allergic to but for whom no safe alternative exists — e.g. penicillin desensitisation, aspirin desensitisation (AERD), chemotherapy or biologic desensitisation. Also covers allergen immunotherapy: SCIT, SLIT, venom VIT, and peanut OIT (Palforzia®).

Eosinophilic Gastrointestinal Disorders

Eosinophilic oesophagitis (EoE), eosinophilic gastroenteritis, and eosinophilic colitis. EoE presents with dysphagia, food bolus obstruction, and heartburn — driven by food allergen-triggered eosinophilic mucosal inflammation. Management involves six-food elimination diet (SFED) or targeted dietary elimination guided by allergy testing, proton pump inhibitors, topical swallowed steroids (fluticasone, budesonide), and — in refractory cases — dupilumab or cendakimab.

Hypereosinophilic Syndromes (HES)

Persistent peripheral blood eosinophilia above 1.5 × 10¹/L for more than 6 months with evidence of eosinophil-mediated organ damage (cardiac, pulmonary, neurological, cutaneous, or gastrointestinal). Classified as myeloproliferative (FIP1L1-PDGFRA fusion — imatinib-responsive), lymphocytic, or idiopathic. Managed with corticosteroids, mepolizumab (anti–IL-5), or targeted agents depending on the underlying mechanism.

Omalizumab (Xolair®)

Anti-IgE

Severe allergic asthma, chronic spontaneous urticaria, nasal polyps (CRSwNP), adjunct to OIT in highly sensitised patients, EAACI 2025: IgE-mediated food allergy

Dupilumab (Dupixent®)

Anti-IL-4Rα

Severe atopic dermatitis, eosinophilic asthma, CRSwNP, EoE, CSU (FDA-approved April 2025), prurigo nodularis

Mepolizumab (Nucala®)

Anti-IL-5

Severe eosinophilic asthma, CRSwNP, EGPA (eosinophilic granulomatosis with polyangiitis), HES, CECA

Benralizumab (Fasenra®)

Anti-IL-5Rα

Severe eosinophilic asthma. Rapid eosinophil depletion; monthly then 8-weekly dosing

Tezepelumab (Tezspire®)

Anti-TSLP

Severe asthma across all phenotypes (eosinophilic and non-eosinophilic). Broadest indication of any respiratory biologic. MHRA-licensed.

IL-1 Inhibitors

Anakinra, canakinumab, rilonacept

Autoinflammatory syndromes (CAPS, TRAPS, HIDS, FMF), HES, and other inflammasomopathies

Lanadelumab (Takhzyro®) & Berotralstat (Orladeyo®)

Plasma kallikrein inhibitors — HAE prophylaxis

First-line long-term prophylaxis for hereditary angioedema. EAACI/WAO 2024 UK Delphi consensus confirmed as standard of care.

Remibrutinib (Rhapsido®)

Oral BTK inhibitor

First oral BTK inhibitor FDA-approved for antihistamine-refractory chronic spontaneous urticaria (2025). Under EMA/MHRA review. Enquire about availability.

Not in scope of specialised service:

• Non-complex allergy (standard hay fever, mild food allergy, mild eczema)
• Chronic fatigue syndrome / ME
• Paediatric patients (these are assessed at our paediatric allergy clinic)
• Food intolerance (non-IgE-mediated)

For these conditions, book a routine appointment:

Our standard allergy clinic can assess and manage the full range of common allergic conditions, including hay fever, standard food allergy (including peanut OIT), mild-to-moderate asthma, eczema, and drug allergy, without the specialised service pathway.

Book a standard allergy appointment →

Self-Referral (Private Patients)

Private patients can self-refer directly without a GP referral letter. Register online, book a specialist immunology and allergy consultation, and bring all available medical records, test results, and correspondence relating to your condition.

Register as a new patient →

GP or Specialist Referral

Referrals from GPs, paediatricians, rheumatologists, haematologists, dermatologists, and ENT surgeons are welcomed. Please include all relevant clinical details, previous investigations, and current medications. NHS England specialised service referral criteria are noted above.

Insurance & referral information →

Transferring Care from Another Centre

Patients relocating to London from other parts of the UK, or from overseas, who are already under specialist immunology or allergy care can transfer their management to us. Please contact us before booking with a summary of your current treatment and the name of your previous centre.

Call to discuss transfer: 020 3143 3449 →

I have recurrent infections. Could this be an immunodeficiency?

Recurrent infections warrant investigation for immunodeficiency particularly if they: affect the same site repeatedly (e.g. sinuses, lungs), are caused by unusual organisms, fail to respond to standard antibiotic courses, require hospital admission, or occur alongside a family history of similar problems. Initial blood tests include full blood count, immunoglobulin levels, and specific antibody responses to vaccines. A consultation with our clinical immunology team is the appropriate next step.

My tryptase is elevated. Does this mean I have mastocytosis?

Not necessarily. Mildly elevated tryptase (up to 11.4 μg/L) may reflect increased mast-cell burden without a formal diagnosis of mastocytosis. Higher tryptase levels, particularly above 20 μg/L, or elevation associated with recurrent unexplained anaphylaxis, urticaria pigmentosa, or bone pain warrants a full specialist assessment including consideration of a bone marrow biopsy and KIT mutation analysis. Our consultants will assess your specific clinical picture.

I have recurrent episodes of abdominal pain and facial swelling but no rash. Could this be hereditary angioedema?

Yes, this is a characteristic pattern of hereditary angioedema. Recurrent angioedema without urticaria, particularly with abdominal attacks (which can mimic a surgical emergency), throat attacks, or a family history, should be investigated urgently with C1 inhibitor level, C1 inhibitor function, and C4 complement level. HAE is life-threatening if undiagnosed and untreated. Please contact our clinic and mention this pattern specifically when booking.

I have severe eczema and asthma that do not respond to standard treatments. Am I eligible for biologic therapy?

Quite possibly. Both severe atopic dermatitis and severe eosinophilic asthma now have multiple licensed biologic options. Dupilumab is licensed for atopic dermatitis, severe asthma, and nasal polyps. Tezepelumab, mepolizumab, and benralizumab are licensed for severe asthma. Eligibility depends on clinical criteria including prior treatment history, eosinophil counts, IgE levels, and quality-of-life impact. Our consultants will conduct a full assessment and arrange joint care with dermatology where needed.

I have a child with a suspected immunodeficiency. Can you see them?

Paediatric immunodeficiency is not managed under this particular specialised adult service. However, our paediatric allergy consultants can assess children with recurrent infections, suspected immunodeficiency, and complex allergic conditions. Please book under our paediatrics service (020 314 33446) so your child is seen by an appropriately trained paediatric specialist.