Elevated serum TARC/CCL17 levels associated with childhood interstitial lung disease with SFTPC gene mutation

To the Editor, Childhood interstitial lung disease (ILD) is a serious and often life‐ threatening disease that causes interstitial lung lesion formation. Several causative genes of childhood ILD, such as SFTPC, SFTPB, and ABCA3, have been identified in some children. The pathogenesis of ILD caused by SFTPC mutations may involve the accumulation of misfolded surfactant protein C (SP‐C) in vesicles, inhibition of pulmonary surfactant reuptake, and decreased expression of SP‐C. However, this pathogenesis remains to be confirmed. Thymus and activation‐regulated chemokine/C‐C motif chemokine ligand 17 (TARC/CCL17) is a known disease marker for atopic dermatitis. Recently, it has been reported that plasma TARC/CCL17 levels were upregulated in patients with idiopathic pulmonary fibrosis compared with those in normal controls. However, to date, there has been no report on the association between childhood ILD and TARC/CCL17. Herein, we report our experience with a case of childhood ILD with SFTPC mutation and elevated TARC/CCL17 levels at disease onset that decreased after patient improvement with treatment. In children with SFTPC mutation, elevated TARC/CCL17 levels may be associated with ILD, which is different from the pathogenesis of atopic dermatitis. Moreover, it was suggested that TARC/CCL17 levels could be used as a biomarker for ILD in patients with SFTPC mutation. An otherwise healthy 15‐month‐old girl was admitted to our hospital for fever, breathing difficulty, and poor oral intake. Nine days before admission, nasal discharge and cough appeared and gradually worsened; subsequently, poor oral intake appeared. No fine crackles were heard. The patient required supplemental oxygen and was admitted to the hospital. She had no history of respiratory impairment at birth. However, the patient had a family history of ILD in her maternal grandmother. Informed consent was obtained from the patient's guardians for the publication of this case report. Laboratory test results showed white blood cell count, 941 × 10/L; neutrophil count, 58%; C‐reactive protein level, 0.01mg/dl; lactate dehydrogenase level, 929 IU/L; Krebs von den Lungen‐6 (KL‐6) level, 909 U/ml (normal range < 500 U/ml); surfactant protein A level, 319 ng/ml (normal < 43.8 ng/ml); and surfactant protein D level, 2770 ng/ml (normal < 110 ng/ml), which were suspicious findings for ILD (Table 1). ß‐D‐glucan level was 7.9 pg/ml (normal < 20 pg/ml) and both IgG and IgM were negative for cytomegalovirus. Chest radiography showed bilateral diffuse ground‐glass opacities (Figure 1). Chest computed tomography scan showed bilateral diffuse frosted shadows (Figure 2), leading to ILD diagnosis. Although prednisolone was started on Day 2 after admission, the patient's respiratory status did not sufficiently improve, and supplemental oxygen therapy was required. Therefore, methylprednisolone (30mg/kg/day) was administered two times for 3 consecutive days on Days 13–15 and 19–21. However, the patient's respiratory status remained poor. Hydroxychloroquine (10mg/kg/ day) was then started on Day 21, and azithromycin (10mg/kg/day) three times a week was started on Day 56. Thereafter, her respiratory status gradually improved. Although posthospitalization treatment improved her hypercapnia and labored breathing, the child was still in need for oxygen therapy administration and could not be weaned off it. On Day 66 after hospitalization, the patient was discharged with home‐based oxygen. Chest X‐rays showed little improvement in imaging findings between admission and discharge (Figure 3). Respiratory status, oxygenation, and laboratory data of ILD markers such as KL‐6 gradually improved after discharge (Table 1). Genetic analysis of SFTPB, SFTPC, ABCA3, CSF2RA, and CSF2RB showed SFTPC mutation and p.I73T (c.218T>C). Therefore, ILD was determined to be caused by this SFTPC mutation. The parents and grandparents of the patient did not wish to undergo genetic testing.