We presented a patient who suffered from multisystem LCH with hypothyroidism and sclerosing cholangitis. He was initially diagnosed and treated for cholestasis but the results of biopsy showed the infiltration of Langerhans cells in the skin and thyroid tissues. The patient had been diagnosed and treated for Hashimoto’s thyroiditis for thyroid hypermegaly three years previously. Further examinations found that LCH also involved his lungs, some nails, and spleen.
LCH can involve any organ system in the body, but the frequency of involvement depends on age(2). Several large retrospective studies consisting of neonates and children under the age of 4 years, showed that 51–71% of children with LCH present with multisystem disease, but 69–72% of adults only involve a single organ(3). A recent report from the International Registry of the Histiocyte Society showed that single-system Langerhans cell histiocytosis was found in 31.4% of patients, 68.6% had multisystem disease, and 29.6% had diabetes insipidus (3–4, 8). Among the multisystem lesions, the involvement of lungs, bones, and skin are common (9). As a result, when a patient shows a multisystem disease, we should be aware of LCH, and if we cannot diagnose the disease according to one organ lesion, we should seek clues from other organs. In this case, the skin biopsy prompted us to the diagnosis of LCH. As a clue to the disease, the following biopsy of the thyroid also reinforced the diagnosis of LCH. Finally, we concluded that the disease involved not only skin and the thyroid, but also liver, lungs, nails and possibly the spleen. A case involving so many organs is rare, especially interfering with the liver, nails, and thyroid.
Because reports about LCH are still limited to case reports, the etiology of LCH must remain speculative. However, it has been suggested that abnormal Langerhans cells elucidate cytokines, such as the platelet-derived growth factor, interleukin 1, and tumor necrosis factor, which may play an important role in the development of hepatic fibrosis (5). This is also presumed to be the mechanism of multisystem clonal infiltration. In our case, the ESR was higher than normal, indicating the active role of the immune reaction and activity of the disease. With disease remission, his ESR level decreased. Calming et al reported that ESR estimates (n = 76) associated with active disease was 21mm/h (SD ± 68.4) (10). An elevated ESR may be a clinically valuable indicator of disease activity in patients with LCH, but the role of ESR, nail, and thyroid involvement as poor prognostic signs are unclear.
During the treatment, the patient did not respond well to Vp-16 and prednisolone chemotherapy. During tapering, the rashes and liver function of the patient relapsed. Then the chemotherapy strategy was changed to VP-16, Prednisone acetate tablets, Cyclophosphamide, and vinblastine following the recommendation of a hematologist. Though the patient developed adverse events such as bacterial infection, combination chemotherapy continued with supportive treatment. According to a report, VP-16 treatment is less efficacious to multisystem LCH. From this case, we learned that primarily using a stronger combination chemotherapy is beneficial and the VP-16 combination with Prednisone acetate tablets is not the best choice in such cases.
The disadvantages of this study are lack of checking of the BRAF V600E mutation and that the follow-up time was relatively short. Previous study reported that the BRCA V600E mutation is related to multiple system involvement, high risk, and relapse of LCH. We will collected a large amount of laboratory data to clarify the correlation between BRAF V600E mutation and ESR changes in LCH patients, and the clinical manifestations and disease prognosis of each system.
Reported LCH related SC progresses more rapidly than other forms of sclerosing cholangitis. Most LCH-related SC patients received liver transplantations at the late stage of fibrosis that is effective (11–13). LCH reoccurrence after transplantation is relatively low. Involvement of the thyroid and nails in multisystem LCH is a sign of poor prognosis. Based on the poor prognostic features of this case, we decided to treat with more aggressive regimens as we thought that might be an effective option of treatment for multisystem LCH.