주기적 고용량 부신피질 호르몬제 투여로 치료된 Castleman 병 1예
A case of Castleman’s disease patient treated successfully with cyclic high-dose steroid therapy
Article information
Trans Abstract
Castleman’s disease is rare, and its cause is unknown. Although various treatments have been attempted, no standard treatment has been established for it.
A 51-year-old male on hemodialysis with end-stage renal disease was admitted to our hospital with fever and myalgia. He was diagnosed with multicentric Castleman’s disease (MCD) of the hyaline vascular type. Considering his underlying disease and general condition, cyclic high-dose steroid therapy (prednisolone 1 mg/kg/day for 5 days) was administered every 4 weeks, eight times in total. After this, no symptomatic manifestations of MCD or signs on computed tomography were observed. We report an immunocompromised patient diagnosed with MCD of the hyaline vascular type, who was successfully treated with cyclic high-dose steroid therapy. (Korean J Med 79:72-76, 2010)
INTRODUCTION
Castleman’s disease (CD) is a lymphoproliferative disorder that was first reported by Benjamin Castleman in 19561). Clinically, this disease is subdivided into unicentric (UCD) and multicentric(MCD) Castleman’s disease. Histologically, it is classified into (1) hyaline vascular (HVV), (2) plasma cell (PCV), and (3) mixed (MV) variants2).
The diagnosis of UCD is likely to be made incidentally in asymptomatic young adults. Histologically, HVV is the most common subtype among patients with UCD, and it is treated by surgical removal3). By contrast, MCD occurs more frequently in males 52 to 65 years old. MCD is accompanied by non-specific general symptoms (fever, night sweats, weight loss, and fatigue) and peripheral lymphadenopathy. It frequently invades other organs, such as the liver, spleen, and kidney. Histologically, PCV is the most common type in MCD4). MCD has a variable clinical course, and most patients with this subtype die of fulminant infection, progressive CD, or related malignancies5).
Steroid therapy and chemotherapy have been attempted for the treatment of MCD, but no standard treatment has yet been established6). We diagnosed this case as HVV MCD, which is a rare subtype constituting less than 10% of all MCD cases. We report a case involving an immunocompromised patient with a diagnosis of MCD HVV who was treated successfully with cyclic high-dose steroid therapy.
CASE REPORT
A 51-year-old male was admitted through the Department of Nephrology outpatient clinic complaining of fever and myalgia. The patient had been undergoing hemodialysis three times a week since he was diagnosed with end-stage renal disease (ESRD) in 2003. He worked as a taxi driver, and his family history was unremarkable. He had smoked for 30 years, but did not drink alcohol.
He complained of a fever, chills, cough, sputum, night sweats, and pain in the left flank. Multiple 1~2 cm lymph nodes were palpated in the left supraclavicular region and bilateral axillary and inguinal regions. They were soft and movable, but not tender. Laboratory findings indicated anemia, with white blood cell count (WBC) of 5,500/mm3, hemoglobin 9.5 g/dL, hematocrit 28.9%, and platelets 155×103/mm3. The peripheral blood smear indicated normocytic normochromic anemia. Further tests for anemia study showed iron 77 μg/dL, total iron binding capacity 87 μg/dL, and ferritin 2,353 ng/mL. These findings indicated anemia of chronic disease. The erythrocyte sedimentation rate (ESR) was 32 mm/hr, and C-reactive protein (CRP) was increased at 5.23 mg/dL. The serum albumin was decreased at 3.2g/dL. Liver function tests were within normal ranges. Creatinine was 5.7 mg/dL, and beta-2 microglobulin was increased at 37.5mg/L.
He underwent chest and abdominopelvic computed tomography(CT) on admission. The chest CT images showed lymph node enlargement in the bilateral supraclavicular, carotid space, axillary, mediastinal, and hilar regions (Figure 1A). The abdominopelvic CT images showed multiple 1~2 cm lymph nodes in the interaortocaval and para-aortic areas and common iliac and inguinal areas bilaterally. No hepatosplenomegaly was observed(Figure 2A).
(A) It manifested both axillary lymph node enlargement before steroid treatment. (B) Both axillary lymph node enlargement were disappeared on follow up chest CT scan in four months after completion of steroid treatment.
(A) Both side multiple inguinal lymph node enlargement were shown before steroid treatment. (B) Both side multiple inguinal lymph node enlargement were disappeared on follow up abdominopelvic CT scan in four months after completion of steroid treatment.
Clinically, because lymphoma was suspected, an excisional biopsy of the inguinal lymph nodes was performed bilaterally. The histological diagnosis was the HVV type of CD. The histological features showed small blood vessels penetrating the germinal center from the vascular perifollicular tissue (Figure 3). Immunohistochemical staining for CD3 and CD20 was positive, whereas that for CD15 was negative. Serum protein electrophoresis showed polyclonal gammopathy. Anti-HIV antibody and human herpes virus-8 (HHV-8) polymerase chain reaction(PCR) from peripheral blood mononuclear cells were negative.
Hyaline-vascular type of Castleman's disease shows that a small blood vessels penetrates the germinal center from the vascular perifollicular tissue (Hematoxylin-eosin stain, A: ×40, B: ×100, C: ×200).
Considering the patient’s underlying ESRD and his general condition (ECOG Score 3), steroid therapy was chosen over chemotherapy. As the patient had ESRD and was on hemodialysis, his underlying disease made it difficult to maintain him on steroids, as he was immunocompromised and prone to infection. Consequently, high-dose cyclic steroid administration was chosen, and the patient was given prednisolone 1 mg/kg/day for 5 days and every 4 weeks.
His symptoms improved with steroid treatment after 2 days. One month later, the lymph nodes seen on chest and abdominopelvic CT had become smaller. Eight cycles of high-dose steroid were administered, and the patient had no symptoms of CD after completing this treatment. In addition, laboratory testing on completion of the treatment showed Hb of 9.6 g/dL and CRP of 6.3 mg/dL. The other results were unremarkable.
The lymphadenopathy found at the time of diagnosis on chest (Fig. 1B) and abdominopelvic (Fig. 2B) CT disappeared. Currently, the patient has been followed as an outpatient for 11 months without recurrence.
Discussion
Castleman’s disease is a rare disorder characterized by non-malignant tumors that develop in the lymphoid system throughout the body. It involves the hyperproliferation of B cells that often produce cytokines, which can produce generalized signs and symptoms. Several variants and clinical subtypes of Castleman’s disease have been identified3). MCD was first reported by Gaba in 1978 and is most common in males 52 to 65 years old4).
Clinically, MCD manifests as non-specific symptoms such as fever, night sweats, weight loss, and fatigue, and it is commonly accompanied by peripheral lymphadenopathy. In 50% of cases, hepatomegaly or splenomegaly is observed. The laboratory findings commonly show anemia, hypoalbuminemia, hypergammaglobulinemia, and elevated ESR. Histologically, PCV and MV are the most common, while HVV occurs in less than 10% of cases5).
The clinical course varies and can be rapidly progressive, chronically persistent, or episodic relapsing5). Fatal complications include fulminant infection, progressive CD, or related malignancies, including Kaposi’s sarcoma, non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, and POEMS syndrome5,7,8). The overall survival period is 28 to 30 months for this clinical subtype, which has a poorer prognosis than UCD does. Our patient showed nonspecific general symptoms, including fever, myalgia, and peripheral lymphadenopathy. HVV was diagnosed histologically.
The etiology of MCD is not clear. Frizzera considered MCD to be a generalized B-cell lymphoproliferative disease, in which plasma cells accumulated continuously, some of which led to clonal proliferation2). In 1997, Grandadam postulated that the exacerbation of symptoms related to MCD was due to an increase in the number of HHV-8 particles in mononuclear cells in peripheral blood9). Specifically, viral IL-6, which corresponds to human interleukin-6, was discovered. It was postulated that viral IL-6 contributed to immune cell activation10). In our case, anti-HIV antibody and HHV-8 PCR from peripheral blood mononuclear cells were both negative.
With respect to treatment, it has been difficult to determine a proper therapeutic modality, as the disease is rare and its clinical course varies. Various treatment methods have been attempted, including surgery, radiation, steroids, anti-viral agents, specific antibodies, cytokine activation inhibitors, and single-agent and combination chemotherapy11).
The current recommendation is aggressive combination chemotherapy like cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) for patients with a good performance state, and maintenance therapy like steroid therapy or single-agent (vinblastine or etoposide) chemotherapy for patients with a poor performance state to improve their symptoms. Steroids are given frequently as systemic therapy. In 1983, Summerfield administered prednisolone 10 and 35 mg/day, respectively, to two HVV MCD patients and tapered these doses to 7.5 and 15 mg/day as maintenance doses. He reported one case each of partial remission (PR) and complete remission (CR)12). In 1985, Frizerra reported PR in all six cases of PCV MCD who had undergone steroid therapy. Weisenburger reported four cases of PR and two cases without remission in six PCV MCD patients8). In 1998, Herrada reported that treatment initiated with prednisolone 1 mg/kg/day followed by maintenance therapy at 20~30 mg/day led to complete remission (CR) in two cases13).
The above authors reported various results for single-steroid therapy for patients with different histological types of MCD. A common feature was that steroid-responders showed recurrence upon tapering or stopping steroid administration.
In our ESRD patient with a diagnosis of HVV MCD, because of concern regarding the risk of infection, cyclic high-dose steroid therapy was administered as a replacement therapy instead of maintenance steroid therapy. A complete remission was achieved after repeating the high-dose steroid regimen eight times. This patient tolerated the regimen well, was comfortable, and was free from adverse effects while the cyclic steroid regimen was being administered. No symptoms developed despite the steroid regimen, and no recurrence occurred. Nevertheless, on-going follow-up is necessary, as the follow-up period has only been 11 months since completion of the treatment in this case.
Based on a review of recently published literature, our case is the first report of complete remission with the administration of a cyclic high-dose steroid regimen in an immunocompro mised HVV MCD patient.
Factors that could influence the results of steroid therapy among MCD patients need to be investigated further. Additional studies on the effects of cyclic high-dose steroid therapy in patients with either a poor performance status or immunocompromised state are necessary in the future.