A 13-year-old girl with T1DM was admitted to our hospital for poor glucose control under multiple daily insulin injections.
A review of her medical history and physical examination at presentation suggested that the girl had been suffering from chronic spontaneous urticaria unresponsive to antihistamine therapy. T1DM was diagnosed at the age of 11, appropriate treatment was initiated (multiple daily insulin injection therapy), and other type 1 diabetes-associated autoimmune diseases (celiac disease, autoimmune thyroiditis, and autoimmune atrophic gastritis) were excluded at diagnosis and yearly follow-up. Two years after the diagnosis of T1DM, she developed severe symptoms of chronic urticaria. Treatment with cetirizine (10 mg/day) was initiated, although no significant response was observed. There was no apparent correlation with exposure to common allergens nor physical stimuli. No history of allergy was reported; in particular, she did not report symptoms of oculorhinitis, asthma, or atopic dermatitis. She only referred one episode of urticaria in early childhood after taking amoxicillin-clavulanic acid.
The timing of onset and the frequency and duration of the hives were not consistent with insulin allergy. Skin tests with insulin were not performed due to the persistence of hives and ongoing antihistamine treatment and the absence of concrete evidence supporting insulin skin test reliability.
Laboratory work-up revealed normal complete blood count and leukocyte formula (mild eosinophilia was detected: 600/mmc, n.v. 0-450) and normal serum total IgE. Specific IgE against common food and inhalant allergens showed weak positivity for only dust mites and ragweed. Liver, kidney, and thyroid function were normal; thyroid autoimmunity (anti-thyroid peroxidase, 11 IU/ml; anti-thyroglobulin, 31 IU/ml; and anti-TSH receptor, <0.8 IU/L) was negative. Celiac disease was also excluded, and inflammatory markers (CRP, ESR) were negative. Screening for other autoantibodies most frequently associated with CSU (ANA and ENA) showed negative results, with the exception of antinuclear antibodies (titer, 1:160). Complement fractions (C3, 1.13 g/L; C4, 0.22 g/L) and immunoglobulin classes were normal. Microbiological tests (including fecal Helicobacter pylori antigen) and stool parasite tests yielded negative results. Streptococcal infection was excluded. Urinalysis was also normal.
Due to treatment failure on standard cetirizine prescription, the dose was increased twofold, with only minimal improvement. We monitored the disease course on a weekly basis with a mean Urticaria Activity Score (UAS) of 36.
Given the persistence of clinical symptoms and the patient's poor quality of life, omalizumab was started at a standard recommended dose of 300 mg intramuscular injection every 4 weeks. After the third dose and concomitant oral antihistamine treatment, symptoms significantly improved (UAS, 14), and only small urticarial elements remained on the extremities. After the sixth dose, CSU symptoms completely subsided, and antihistamine treatment was suspended ( Figure 1 , picture before and after treatment). Treatment was completed after 11 administrations of omalizumab with no relapsing CSU to date.
Glucometric data derived by flash glucose monitoring during treatment is shown in  Table 1 . Time spent in specific glucose ranges at baseline and after treatment were compared by chi-squared test. From baseline, time below range (TBR) has shown a slight but statistically significant reduction. However, this improvement has been apparently at the expense of an increased time above range (TAR) of 180-250 mg/dl. Time in range (TIR) did not vary. Baseline and post-treatment HbA1c were 6.8% and 6.9%, respectively, showing a substantial stable average glucose control during the treatment period. Daily insulin doses also did not vary significantly and were 1.1 U/kg at baseline and 0.9 U/kg post-treatment.