1. Lymphadenopathy in SLE
Division of Rheumatology
R4 송 란

2. Pyrexia
&
lymphadenopathy

3. (Lymphocyte dominant)
35-year-old, male
Moderate-grade, intermittent fever, weight loss (10 kg /3 months)
No history of skin rash, photosensitivity, arthritis, oral ulcer, alopecia,
urinary,bowel complaints
P/Ex.
V/S> BP 130/80 mmHg- PR 110/min-RR 22/min-39°C
lymph nodes : multiple, 1-cm, nontender, firm, Cervical & axillary regions
left pleural effusion and hepatosplenomegaly
- Rheumatol Int.2005;25
Initial laboratory data (CBC/DC, ESR,Urinalysis, electrolytes,
coagulation profile, kidney and liver function tests): normal
Exudate
(Lymphocyte dominant)
Chest X-ray : Lt.hilar lymphadenopathy, pleural effusion
ANA : negative, anti-dsDNA antibody: within normal limits
Mantoux test: 12-mm induration
Cervical lymph node biopsy : reactive follicular hyperplasia
BM biopsy: No granuloma, AFB & fungus staining(-)
Liver biopsy: normal
Tuberculosis  empirical anti-Tb therapy
Pancytopenia, direct Coomb’s test(+)
ANA: positive(1:320), homogenous pattern, low C3,
anti-dsDNA: positive
Proteinuria, hematuria Kidney Bx.: Lupus nephritis class IV

4. Cause of peripheral lymphadenopathy
Examples
Infections
Bacterial Localized
Generalized
Streptococcal pharyngitis; skin infections; tularemia; plague; cat scratch disease; diphtheria; chancroid;
Brucellosis; leptospirosis; lymphogranuloma venereum; typhoid fever
Viral
HIV; EB virus; herpes simplex virus; CMV; mumps; measles; rubella; hepatitis B
Mycobacterial
Mycobacterium tuberculosis; atypical mycobacteria
Fungal
Histoplasmosis; coccidioidomycosis; cryptococcosis
Protozoal
Toxoplasmosis; Leishmaniasis
Spirochetal
Secondary syphilis; Lyme disease
Cancer
Metastatic; lymphoma; leukemia
Lymphoproliferative
Angioimmunoblastic lymphadenopathy with dysproteinemia
Autoimmune lymphoproliferative disease
Rosai-Dorfman's disease
Hemophagocytic lymphohistiocytosis
Immunologic
Serum sickness; drug reactions (phenytoin)
Endocrine
Hypothyroidism; Addison's disease
Miscellaneous
Sarcoidosis; amyloidosis; histiocytosis; chronic granulomatous diseases; Castleman's disease; Kikuchi's disease; Kawasaki disease; systemic lupus erythematosus; RA; Still's disease; dermatomyositis

5. Total 82 patients
During the first year of the clinic

6. Frequency of symptoms of systemic lupus erythematosus
Percent at onset
Percent at anytime
Fatigue 50
74-100
Fever 36
40-80
Weight loss 21
44-60
Arthritis or arthralgia
62-67
83-95
Skin 73
80-91
Raynaud's phenomenon
17-33
22-71
Renal
16-38
34-73
Gastrointestinal 18
38-44
Pulmonary
2-12
24-98
Cardiac 15
20-46
Lymphadenopathy
7-16
21-50
Splenomegaly 5
9-20
Hepatomegaly 2
7-25
Central nervous system
12-21
25-75
Von Feldt et al. Postgrad Med 1995; 97

7. Evaluation of peripheral lymphadenopathy in SLE
Characteristics of lymph nodes
Soft
Nontender
Discrete
Size : 0.5 ~ several centimeters
Location : cervical, mesenteric, axillary, inguinal areas – M/C
hilar, mediastinal, retroperitoneal - unusual
Lymph node enlargement
Onset of disease
Exacerbation
Result of infection  tender
Lymphoproliferative disease in SLE

8. Pathology of Lymph Node in Lupus
Follicular hyperplasia and necrosis
Castleman’s disease, T-zone dysplasia with hyperplastic follicles,
Nonspecific follicular hyperplasia
Hematoxylin bodies(LE cell)

9. Differential Diagnosis of Lymphadenopathy in SLE
Chronic infectious disorder
Viral or bacterial infections
Tuberculosis
Lymphoproliferative disorder
Lymphoma
Castleman’s disease
Sarcoidosis
Kikuchi’s disease
Negative serological tests for virus
Blood, urine, tissue culture: negative
PPD test : negative
LN biopsy: absence of granuloma with caseous necrosis
BM biopsy or LN biopsy
: presence of neoplastic lymphoid cell
LN biopsy : absence of granuloma
LN biopsy : patchy, paracortical necrotizing process with prominent histiocytes, absent neutrophil, hematoxylin body and rare plasma cell

10. Y.Shapira et al. Clinical rheumatology,1996; 15

11. Lymphadenopathy: significantly younger than non-lymphadenopathy
(age 36.2 ± 3.0 vs ± 1.9 years, p = 0.012)
No difference : sex ratio, education, ethnic origin
Y.Shapira et al. Clinical rheumatology,1996; 15

12. Malignant Lymphoma - Non-Hodgkin Lymphoma -

13. Glucocorticoid therapy  intermittent spiking night-time fever
37-year-old, Female
Heavy proteinuria, microscopic hematuria, malar rash, leukopenia,
lymphopenia, painless elastic LN(<1cm) on Rt. Neck, tender firm
LN(1cm) on Lt. groin
ANA, direct Coombs’ test, lupus anticoagulant Ab, anticardiolipin Ab.
 positive
Renal Bx.: lupus nephritis-membranous glomerulonephritis(MGN)
Glucocorticoid therapy
 intermittent spiking night-time fever
progressive LN enlargement over neck and groin
 LN bx.: EBER-1 positive Diffuse large B-cell lymphoma(DLBL)
NHL(DLBL) presenting with SLE and MGN
Ming-Hsien Lin et al. Lupus, 2003; 12

14. RE pooled SIR for SLE of 7.4  7.4-times increase in the incidence
- Elias Zintzaras et al.Arch Intern Med. 2005;165
Figure. Standardized incidence rate (SIR) estimates of development of non-Hodgkin lymphoma with the corresponding 95% confidence intervals of studies included in the meta-analysis for systemic lupus erythematosus (SLE)
= 7.4
RE pooled SIR for SLE of 7.4  7.4-times increase in the incidence
126 cases per 100,000 patient-years

15. 9547 subjects with definite SLE
23 clinical center
Canada, America, the UK
(England and Scotland), Sweden, Iceland, Korea
9547 subjects with definite SLE
NHL: 42 cases
Mean age: 55.3 years
Average SLE duration: 6.7 years
22 (52%) of the 42 cases: death
Median of 1.2 yrs after lymphoma Dx.
Total NHL(n) 21
DLBL(%)
11(52)
Small lymphocytic(%)
4(19)
Follicular(%)
3(14)
Burkitt’s 1
Peripheral T cell
MALT

16. Kikuchi-Fujumoto Disease

17. Kikuchi-Fujimoto's disease (KFD)
Histiocytic necrotizing lymphadenitis, Young women
Symptoms : upper respiratory tract infection
Fever, leukopenia : 50 % of patients
Lymphadenopathy: cervical - M/C
Benign and self-limited lymphadenitis
LN biopsy
Necrotising lymphadenitis (cortical and paracortical area)
Hematoxylin bodies, neutrophil  absent
Mahajan et al. Proc (Bayl Univ Med Cent) 2007;20

18. KFD associated with SLE
Shares clinical features: arthralgia, fever, leukopenia, lymphadenopathy
Common hyperimmune reaction
directed against different antigenic stimuli
MEDLINE and LILACS database
KFD associated with SLE: 35 cases
Santana et al. Clin Rheumatol 2005; 24

19. Hemophagocytic syndrome

20. Hemophagocytic syndrome
Histiocytic reactive process of strong immunologic activation, such
as Severe infection, malignancy, autoimmune diseases, and
Metabolic diseases
Diagnosis : 5 out of the 8 criteria
Fever
Splenomegaly
Bicytopenia
A. Hb <9.0 g/dL (In infants <4 weeks: Hb <10.0 g/dL)
B. Platelets (<100x109/L)
C. Neutrophils (<1.0x109/L)
Hypertriglyceridemia and/or hypofibrinogenemia
: fasting TG >265 mg/dL, fibrinogen ≤1.5 g/L
Hemophagocytosis in bone marrow, spleen, or lymph nodes
: no evidence of malignancy
Low/absent NK-cell activity
Hyperferritinemia and/or high sCD25

21. Clinical Presentation
High fever, lymphadenopathy, hepatosplenomegaly, coagulopathy
organ system dysfunction (especially skin, liver, CNS)
High mortality
Laboratory features
Pancytopenia (especially leukopenia), low ESR, high ferritin
low fibrinogen, elevated liver enzymes
Morphologic features: macrophages hemophagocyting blood cells
Incidence
Unknown : very rarely diagnosed (missed in many cases)
Hemophagocytic syndrome combined with necrotizing
lymphadenitis : 8 cases (~2003 yr)
2 patients : systemic lupus erythematosus
Kim et al.J Korean Med Sci 2003; 18

22. Clinical Suspicion
Pathologic Finding