|Year : 2015 | Volume
| Issue : 4 | Page : 925-927
Juan-Ron fever: A rare case report
Sourya Acharya1, Samarth Shukla2
1 Department of Medicine, JN Medical College, DMIMS University, Sawangi (Meghe), Wardha, Maharashtra, India
2 Department of Pathology, JN Medical College, DMIMS University, Sawangi (Meghe), Wardha, Maharashtra, India
|Date of Web Publication||15-Feb-2016|
Department of Medicine, JN Medical College, DMIMS University, Sawangi (Meghe), Wardha - 442 004, Maharashtra
Source of Support: None, Conflict of Interest: None
Juan-Ron fever named after Juan Rosai and Ronald Dorfman is the fever associated with Rosai-Dorfman disease also known as sinus histiocytosis with massive lymphadenopathy (SHML). It is a rare disorder of unknown etiology that is characterized by abundant macrophages in the lymph nodes throughout the body. Usually patient presents with painless lymphadenopathy. We present a case of a 45-year-old male who presented to us with bilateral cervical lymphadenopathy and fever, later on diagnosed to have SHML.
Keywords: Histiocytes, lymphadenopathy, Rosai-Dorfman disease, sinus histiocytosis with massive lymphadenopathy
|How to cite this article:|
Acharya S, Shukla S. Juan-Ron fever: A rare case report
. J Can Res Ther 2015;11:925-7
| > Introduction|| |
Rosai-Dorfman disease (RDD) or sinus histiocytosis with massive lymphadenopathy (SHML) is a rare disorder that typically manifests as lymphadenopathy and systemic symptoms.  Sometimes systemic symptoms may resemble the B symptoms of lymphomas. The characteristic histopathologic feature of the lymph node shows lymphophagocytosis or emperipolesis, and immunohistochemistry shows S100 protein positivity.
| > Case report|| |
A 45-year-old male presented with a history of intermittent fever since 2 months and progressively increasing painless masses in the neck over a period of 1-month duration. The fever was associated with drenching night sweats. There was no history of any significant weight loss. There was no history of cough, breathlessness, abdominal pain, bone pains, fatigue.
On examination, his vitals were stable. He was febrile. Pallor and bilateral cervical and axillary lymphadenopathy was present. The lymph nodes were firm, nontender, approximately 2-3 cm in size, mobile and discrete. There was no sternal tenderness. Other systems examination was normal.
Hematological investigations revealed hemoglobin - 8 g/dL (12-16 g/dL), total leukocyte count - 9600/mm 3 (4000-11,000/mm 3 ), differential leukocyte count - P82, L8, M9, E1, platelets - 2.16 lacs/mm 3 (1.5-4), PS - mild anisocytosis with hypochromia, erythrocyte sedimentation rate (ESR) - 98 mm in 1 st h (0-20 mm in 1 st h). Blood culture did not grow any organism. Elisa for HIV was negative. Mantoux test was negative. Ultrasonography abdomen was normal. Computed tomography scan of chest and abdomen was normal. Histopathological examination of a left cervical lymph node biopsy displayed dilated sinuses in the parenchymal region with extensive infiltration consisting of macrophages and chronic inflammatory cells [Figure 1]. A large number of lymphocytes could be seen in the cytoplasm of macrophages suggesting lymphophagocytosis - emperipolesis [Figure 2]. Lymphoid follicles were hypertrophied and showed the germinal activity.
|Figure 1: H and E, ×40 slide predominant lymphohistiocytic population with the central area showing lymphophagocytosis (empripolesis, black arrow) in the cytoplasm of histiocyte|
Click here to view
|Figure 2: IHC (Dako kit), ×40 view showing S100 protein positive histiocytes (predominantly nuclear with occasional cytoplasmic positivity)|
Click here to view
Immunohistochemical staining of macrophages was positive for S100 protein gene product expression. In view of the above-mentioned observations diagnosis of RDD or SHML was made.
A trial of oral prednisolone in a dose of 40 mg/day was started. There was a dramatic response in form of disappearance of fever and significant decrease in the size of the lymph nodes occurred in 1-week of therapy. The patient was discharged with a steroid taper over next 2 weeks and is awaiting follow-up.
| > Discussion|| |
Although RDD may occur in any age group, it is most frequently seen in children and young adults.  RDD is rare in Indian population with less than a dozen cases being reported in children and none in adults.  This is the rarest case of RDD, which manifested in an adult. Males are commonly affected.  RDD has been reported following bone marrow transplant for precursor-B acute lymphoblastic leukemia, and concurrently, or after Hodgkin's and nonHodgkin's lymphoma.  It is stated that various conditions ranging from autoimmune diseases, hematological malignancies, and viral infections especially with Epstein-Barr virus trigger a cytokine-mediated migration of monocytes leading to macrophages accumulation and activation. However, there is no strong evidence for this at the moment. ,
The most frequent clinical presentation of RDD is a massive bilateral and painless cervical lymphadenopathy with fever, night sweats, and weight loss. Mediastinal, inguinal, and retroperitoneal nodes may also be involved. Extra nodal involvement by RDD has been documented in 43% of cases with the most frequent sites being skin, soft tissue, upper respiratory tract, multifocal bone, eye, and retro-orbital tissue with lymphadenopathy, or as an isolated initial manifestation of disease. Other sites include the urogenital tract, breast, gastrointestinal tract, liver, pancreas, and lungs. Head and neck involvement has been reported in 22% of cases, most commonly the nasal cavity followed by the parotid gland. As in our case conditions such as lymphoma, leukemia, tuberculosis, sarcoidosis, HIV, and infectious mononucleosis that presents with fever and lymphadenopathy have to be ruled out.
Biopsy in such cases is the next best step. The differential diagnosis of a chronic inflammatory infiltrate containing numerous large macrophages includes granulomatous diseases such as Wegener's granulomatosis, sarcoidosis, Hodgkin's disease, and Langerhans' cell histiocytosis (LCH). The classical finding of emperipolesis (active penetration by a smaller cell into or through a larger cell) differentiates it from other diseases.  SHML cells constantly express the S100 protein which differentiates it from lymphomas and LCH. ESR is elevated in 88.5% of cases of RDD and was raised in this case too.
Rosai-Dorfman disease patients can be subdivided into three categories:
Active management of RDD is not required unless the disorder becomes organ or life threatening since it is mostly self-limiting. There is sometimes a dramatic response to oral short course prednisolone in steroid responsive RDD as in this case.  If required, in multimodal and extra nodal systemic disease vinca alkaloid in conjunction with an alkylating agent and corticosteroid provides the most efficient chemotherapeutic regimen besides radiation therapy which is also used. 
- Patients with only lymph nodes that enlarge suddenly with spontaneous regression and without any further recurrences
- Patients with immunologic abnormalities at presentation who have a more widespread nodal disease and a higher fatality rate 
- Patients with several extra nodal site involvement, multimodal disease and a protracted clinical course with multiple relapses and remissions for years. In these cases, the severity of the disease depends on the type and number of extra nodal sites. 
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Rosai J, Dorfman RF. Sinus histiocytosis with massive lymphadenopathy. A newly recognized benign clinicopathological entity. Arch Pathol 1969;87:63-70.
Juskevicius R, Finley JL. Rosai-Dorfman disease of the parotid gland: Cytologic and histopathologic findings with immunohistochemical correlation. Arch Pathol Lab Med 2001;125:1348-50.
Foucar E, Rosai J, Dorfman R. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): Review of the entity. Semin Diagn Pathol 1990;7:19-73.
Lauwers GY, Perez-Atayde A, Dorfman RF, Rosai J. The digestive system manifestations of Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy): Review of 11 cases. Hum Pathol 2000;31:380-5.
Ambati S, Chamyan G, Restrepo R, Escalon E, Fort J, Pefkarou A, et al.
Rosai-Dorfman disease following bone marrow transplantation for pre-B cell acute lymphoblastic leukemia. Pediatr Blood Cancer 2008;51:433-5.
Lu D, Estalilla OC, Manning JT Jr, Medeiros LJ. Sinus histiocytosis with massive lymphadenopathy and malignant lymphoma involving the same lymph node: A report of four cases and review of the literature. Mod Pathol 2000;13:414-9.
Tsang WY, Yip TT, Chan JK. The Rosai-Dorfman disease histiocytes are not infected by Epstein-Barr virus. Histopathology 1994;25:88-90.
McClain LK, Natkunam Y, Swerdlow HS. Atypical cellular disorders. Hematology 2004;1:283-322.
Antonius JI, Farid SM, Baez-Giangreco A. Steroid-responsive Rosai-Dorfman disease. Pediatr Hematol Oncol 1996;13:563-70.
Komp DM. The treatment of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). Semin Diagn Pathol 1990;7:83-6.
[Figure 1], [Figure 2]