On 2 July 2023, a 57-year-old man was admitted to our hospital with recurrent pruritic hives on his lower extremities (Figure 1A) lasting 3 days and chronic arthralgia and bone pain. His medical history included food allergies for 20 years, chronic idiopathic urticaria (CIU) for 5 years, and his family history was unremarkable for autoimmune disorders. He experienced two to three relapses annually, which were managed with corticosteroids and antihistamines. He received two courses of subcutaneous omalizumab (Xolair, Genentech, US) at a dose of 15 mg every 10 days for 3 months in 2019 and 2020. However, his symptoms recurred 3 months after stopping the medication. Upon examination, his vital signs were normal. There were several pale-rose, slightly elevated papules and plaques, measuring 3–6 cm in diameter, on his lower extremities, particularly in his left groin (Figure 1A). He had no enlarged lymph nodes or hepatosplenomegaly. He had some bone pain and tenderness on vertebral percussion. Initial laboratory tests showed a WBC count of 4,100 cells per microliter (PMN = 68%, Lymph = 25%, Eos = 4%. Mono = 3%), an Hb level of 14.1 mg/dL, a Platelet count of 245 (× 10⁹/L), and normal electrolytes, liver function, kidney function, and thyroid function tests, except for a CRP level of 18 mg/dL and a first-hour ESR of 48 mm/h. Additional tests, including HIV, hepatitis B and C, and stool examination, were normal. His serum IgM level increased more than threefold above the upper limit, to 780 mg/dL. The rheumatologic screening tests requested by rheumatology consultations, including ANA, anti-dsDNA, Indirect Immunofluorescence, and RF, revealed no notable findings. Likewise, serum and urine electrophoresis results ordered by hematology consults were also unremarkable.

After local anesthesia, our dermatologist performed a punch biopsy of the right thigh lesion. The histopathological study of the dermal lesion revealed mild interstitial edema, with neutrophils clustered near the vasculature and within the interstitial space, without vasculitis (Figures 1B,C). We diagnosed SchS based on the Strasbourg criteria. Our dermatologist prescribed anakinra. However, due to limited access to the drug, we had to substitute it with prednisolone 0.5 mg/kg daily, colchicine 3 mg/d, and loratadine for 7 days to relieve his symptoms. We then tapered the prednisolone to mitigate its side effects. After 5 days, he was discharged on prednisolone 10 mg/day, colchicine 1 mg/day, methotrexate 7.5 mg/week, montelukast 10 mg daily, loratadine 5 mg daily, and calcium and vitamin D supplements. The patient adhered to the treatment regimen without experiencing a clinical relapse during the first 12 months of follow-up. Although bone pain persisted, it was less severe. One month after discharge, inflammation control tests (ESR and CRP) decreased to normal levels.

A 50-year-old male patient with a history of major depressive disorder, CIU, arthralgia, and peptic ulcer disease spanning 5 years, presented with extensive, pruritic urticaria affecting the abdomen, groin, and back, accompanied by angioedema lasting for 2 days as of 19 March 2024. Additionally, he reported hypertension, non-alcoholic fatty liver disease, polyarthralgia, and generalized bone pain, predominantly in his knees and vertebral column, as well as peptic ulcer disease. He also experienced a respiratory viral infection 2 weeks prior. His mother had asthma and chronic sinusitis. The patient had been treated with long-term corticosteroids, antihistamines, and one course of Xolair over a three-month period in 2022; however, the urticaria recurred 4 months later. At presentation, he exhibited severe pruritic urticaria, arthralgia, mild shortness of breath, and neck pain. His vital signs included a temperature of 38.1 °C, a respiratory rate of 18 breaths per minute, and an oxygen saturation level of 93% on room air. Physical examination showed mild angioedema, large pale-rose urticaria, and palpable plaques with a diameter of 1–7 cm on his abdomen, groin, and back (Figures 2A–C), mild wheezing in both lungs on auscultation, and cervical spine tenderness (Figure 3). He also had a depressed mood. Initial laboratory results indicated a WBC count of 9,800 cells per milliliter (PMN = 72%, Lymph = 20%, Eos = 8%), a Hb level of 12.9 mg/dL, a Platelet count of 381 (× 10⁹/L), ALT = 68, AST = 44 IU/mL, a CRP level of 18 mg/dL, and a first-hour ESR of 48 mm/h. Other laboratory parameters, including FBS = 115 mg/dL, TG = 186 mg/dL, and Cholesterol = 235 mg/dL. The serum electrolytes, BUN, Creatinine, thyroid function tests, HIV, HBV, HCV antibody, and stool examination for occult blood or parasitic infections were all normal. Furthermore, chest computed tomography revealed mild paratracheal opacity, and abdominal ultrasound showed no signs of lymphadenopathy or hepatosplenomegaly, except for a grade II fatty liver. Influenza and SARS-CoV-2 PCR tests were negative. The rheumatologic screening tests, including ANA, anti-dsDNA, RF, serum, and urine electrophoresis, revealed no notable findings. The serum immunotyping capillary electrophoresis test indicated monoclonal gammopathy of IgM (IgM = 648 mg/dL).

Our dermatologist performed a punch biopsy from the thigh lesion with local anesthesia. The histopathology examination revealed neutrophilic infiltrates and mild dermal papillary edema, with no clear vasculitis (Figures 2D,E). Based on the patient’s clinical presentation, laboratory findings, and histological characteristics of the dermal lesion, a diagnosis of SchS was established. Initial treatment consisted of intravenous antibiotics, prednisolone at a dosage of 0.5 mg/kg, tapered over 5 days, bronchodilators, colchicine at 3 mg daily, antihistamines, and consultations with both a rheumatologist and a hematologist. Additionally, our dermatologist recommended the use of anakinra; however, the patient was unable to procure this medication at the time of this report. On the fifth day, the patient was discharged with a prescribed medication regimen, as accepted by him, including oral prednisolone 10 mg daily, colchicine 1 mg daily, montelukast 10 mg daily, loratadine 5 mg daily, duloxetine 60 mg daily, as well as vitamin E, metformin 500 mg daily, calcium, and vitamin D supplements. The patient’s inflammatory biomarkers, including ESR and CRP, normalized 3 weeks after discharge, and the prednisolone dose was reduced to 5 mg/day, which was continued at this dose. During a six-month follow-up period post-discharge, the patient reported no recurrence.

Our main limitation was the unavailability of immunohistochemical staining for the patients’ dermal lesions and the lack of access to interleukin-1 inhibitor drugs, which are considered the most effective treatment options for Schnitzler syndrome in our patients.