Australian Doctor 3rd November 2023 3rd Nov 23 | Page 25

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are generally considered safe . Loratadine is typically the preferred first-line agent . 60-62 Prospective and retrospective registry data have shown omalizumab is safe in pregnancy . 63

In the elderly , management decisions for urticaria must consider drug reactions , comorbidities and organ insufficiency . Choosing a second-generation antihistamine is particularly important in this group as these do not cross the blood – brain barrier . First-generation antihistamines can worsen postural hypotension , urinary retention and arrhythmias . 64 Levocetirizine requires dose adjustment in renal insufficiency . Omalizumab is an effective and safe choice in the elderly . 65

PROGNOSIS

MOST cases of urticaria have a favourable prognosis . H1-antihistamines are effective in reducing symptoms , and most underlying aetiologies undergo natural resolution . The total duration of chronic spontaneous urticaria is variable , with the median duration from one prospective cohort reported as four years . 66 Data from previous observational studies showed the range of observed remission rates at five years to be between 34 % and 45 %.

Possible poor prognostic factors from that review included severity of urticaria at onset and evidence of autoimmunity . 13 The prognosis of acute urticaria is excellent , with most cases resolving without treatment or extensive investigation . In the smaller proportion of cases where an allergic cause is identified , avoidance of the trigger

1 . Which THREE may be features of urticaria ? a Erythematous superficially oedematous plaque lesions . b Affected skin returns to normal without scarring — typically within 30 minutes to 24 hours . c Skin eruption is also associated with angioedema . d Affects skin but not mucous membranes .

2 . Which ONE is not a differential diagnosis of urticaria ? a Urticarial vasculitis . b Facial lymphoedema . c Mast cell activation syndrome . d Autoimmune progesterone dermatitis .

3 . Which TWO statements regarding the epidemiology of urticaria are correct ? a Chronic urticaria is equally common in men and women . b The average duration of acute urticaria is less than one week . c The most common presentation of chronic urticaria is angioedema alone . d Chronic spontaneous urticaria is associated with a subsequent increased incidence of systemic autoimmune disease .

4 . Which THREE drug classes should result in good disease control .

THE FUTURE

PATIENTS invariably ask their treating clinicians what causes their chronic urticaria . The answer remains elusive in most cases , and research groups continue to probe the underlying pathogenesis . Numerous other therapies are also under development for refractory cases . 67 New approaches targeting the mast cell include inhibiting activation signals , activating inhibitory receptors and depleting mast cell numbers ( see box 3 ).

CASE STUDIES

Case study one

JASON , a 21-year-old man , presents to ED with a three-day history of migratory pruritic rash . He is concerned about having allergic reactions but there are no new food or environmental triggers . His only other symptom is watery diarrhoea , which has been occurring for four days and is now starting to resolve . There is no history of atopy or autoimmunity .

On examination , there is sparse urticaria on his trunk . Clinical examination , including vital signs , is otherwise normal . Laboratory investigations show a normal FBC , LFTs and renal function . CRP is slightly raised at 10mg / L ( normal : less than 5mg / L ). A stool culture is collected . He is treated with loratadine 10mg in the ED and subsequently discharged as the urticaria starts to fade .

Jason presents to his GP two days

may cause non-histaminergic angioedema ? a ACEIs . b Dipeptidyl peptidase IV inhibitors . c Vitamin D . d Neprilysin inhibitors .

5 . Which TWO statements regarding the clinical assessment of urticaria are correct ? a Most subtypes of urticaria can be distinguished on morphological examination . b URTI is the most common trigger of urticaria . c Systemic symptoms suggestive of respiratory or cardiovascular compromise should not typically be present in cholinergic urticaria . d Chronic spontaneous urticaria is readily identified on history , with patients describing a temporal relationship to eliciting triggers .

6 . Which THREE investigations

Box 3 . New approaches for treating urticaria

• Recognition of the importance of type 2 cytokines in the pathogenesis of chronic spontaneous urticaria has led to studies with dupilumab ( targeting interleukin ( IL ) -4/ IL-13 ). 68

• Monoclonal antibodies directed against the alarmins IL-25 , IL-31 and thymic stromal lymphopoietin are underway .

• Inhibiting Bruton ’ s tyrosine kinase , located downstream of the IgE receptor , inhibits the activation of mast cells following IgE cross-linking . Fenebrutinib has shown promising results in a phase II study . 69

• Mast cells express G protein – coupled receptors , which when activated , lead to mast cell activation and degranulation . G protein – coupled receptors are another target for monoclonal antibody development .

• Most receptors on mast cells are activating , but there are some receptors that mediate inhibitory signals . Binding of agonists to these receptors inhibits degranulation . One such receptor is the Siglec-8 receptor , for which monoclonal agonists are under development .

• Mast cells express Kit , the receptor for stem cell factor ( SCF ) in the mature state . SCF is essential for differentiation , activation , migration , proliferation and survival of mast cells . Anti-SCF / anti-Kit antibodies could reduce the number of mast cells and inhibit their activation .

Source : Casale TB 2022 68 , Metz M et al 2021 69

later , worried about more pruritic weals that have appeared on his back . Each weal appears for a few hours at a time and is intensely pruritic before fading . The diarrhoea has now resolved . There have been no episodes of angioedema . There is no fever or other reported symptoms on systems review .

The GP reviews the results from the recent ED presentation , and the stool microbiology is positive for norovirus . The GP makes a diagnosis of acute urticaria secondary to viral infection and reassures Jason that this is likely to resolve . The GP prescribes loratadine 10mg daily and instructs him to take a

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may be appropriate in suspected urticaria ? a A wide panel of specific IgE ( previously known as RAST ) tests . b FBC , inflammatory markers and viral respiratory swab . c Skin-prick testing . d Provocation testing .

7 . Which TWO non-pharmacological measures may be appropriate in managing urticaria ? a Avoiding trigger factors . b Instituting a low-histamine diet . c Avoiding NSAIDs and opiates in patients with chronic spontaneous urticaria . d Prescribing an adrenaline autoinjector in all patients with CIndU .

8 . Which THREE medications are preferred in the management of urticaria ? a First-generation antihistamines . b Second-generation

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• RACGP points are uploaded every six weeks and ACRRM points quarterly . further 10mg for any breakthrough urticaria .

Jason attends for a follow-up appointment one week later , and the urticaria has resolved .

Case study two

Divya , a 42-year-old woman , presents to her immunologist with a ninemonth history of recurrent pruritic rash . She describes the rash as raised and pruritic , with transient and variable distribution over her body . She produces photographs that show multiple weals over her abdomen , with a morphology consistent with urticaria .

The urticaria has occurred most

URTICARIA IN ADULTS

antihistamines . c H2-receptor antagonists . d Anti-IgE therapy .

9 . Which TWO statements regarding urticaria in special populations are correct ? a In the elderly , management decisions must consider drug reactions , comorbidities and organ insufficiency . b In pregnant and lactating women , first-generation oral antihistamines are generally considered safe . c Second-generation antihistamines can worsen postural hypotension , urinary retention and arrhythmias . d Omalizumab is an effective and safe choice in the elderly .

10 . Which THREE statements regarding the prognosis of urticaria are correct ? a Most cases of urticaria have a poor prognosis . b Higher income is associated with higher rates of remission in chronic urticaria . c Most cases of acute urticaria resolve without treatment or extensive investigation . d Avoidance of the trigger , if identified , should result in good disease control . days of the week for the past month and has interfered with her sleep . There have been two episodes of periorbital angioedema in the past six months , both improving with H1-antihistamine . Divya has a history of hypothyroidism , for which she takes thyroxine . There is a family history of a similar rash in her sister , who previously had hives as a young adult .

Divya has trialled several H1-antihistamines and is currently taking loratadine 10mg twice daily . Her immunologist prescribes nizatidine ( 150mg twice daily ), increases the loratadine 20mg twice daily and asks Divya to complete a UAS-7 score sheet for the next review .

Divya returns two weeks later reporting only mild improvement in the urticaria . The immunologist makes a PBS application for omalizumab , and Divya returns to the clinic the following week for her first dose .

At follow-up three months later , the urticaria has improved , as evidenced by her UAS-7 score . She is confidently self-administering omalizumab and has had no reactions . Breakthrough urticaria continues to occur approximately once a fortnight , and Divya takes two tablets of loratadine during these episodes , resulting in resolution .

CONCLUSION

URTICARIA is a common condition in adults , with a variety of underlying aetiologies . Classifying urticaria by duration is useful when considering associated causes . GPs can manage most cases of urticaria with patient education and second-generation antihistamines . Specialist referral is indicated for severe cases with persistence despite first-line therapy .

Autoimmune and autoallergic mechanisms have been identified , but there is still considerable work to be done in elucidating the pathogenesis of CIndU and chronic spontaneous urticaria . A definite cause is not found in most patients , and symptomatic treatment is implemented .

Several effective treatments that suppress disease activity can be used in combination to achieve complete disease control in most cases .

RESOURCES

• Australasian Society of Clinical Immunology and Allergy : Chronic spontaneous urticaria information for health professionals bit . ly / 3MQUDlx

• Australasian Society of Clinical Immunology and Allergy : Urticaria patient information bit . ly / 45zT3M9

• Chronic urticaria quality of life questionnaire : bit . ly / 45zaAUH

FURTHER READING

• Allergy 2021 ; 18 Sep . pubmed . ncbi . nlm . nih . gov / 34536239 /

• Nat Rev Dis Primers 2022 ; 15 Sep . nature . com / articles / s41572- 022-00389-z

• Allergol Select 2021 ; 12 Feb . pubmed . ncbi . nlm . nih . gov / 33615122 /

References Available on request from howtotreat @ adg . com . au