Yonago Acta medica 1999;42:131–134

Chronic Fatigue Syndrome and IgA Nephropathy Occurring in the Same
PatientKiyotaka Kohama
Second Department of Internal Medicine, Faculty of Medicine, Tottori University, Yonago 6830826, Japan
We report a patient with a rare association of chronic fatigue syndrome (CFS) and IgA
nephropathy (IgAN). The patient was a 45-year-old woman who presented initiallywith biopsy proven IgAN and 2 years later developed CFS. Because of proteinuria andhematuria, she was referred to our clinic. A renal biopsy done at that time revealed
IgAN. Then she was struck by the sudden onset of profound fatigue. According tocriteria published by the Centers for Disease Control and Prevention in the UnitedStates, we diagnosed her illness as CFS.
Key words: chronic fatigue syndrome; IgA nephropathy; chinese herbal medicine; immunology

Chronic fatigue syndrome (CFS) is characterized by a principal complaint of severe fatigueof at least 6 month’s duration. No single pathogenic mechanism has been consistently identified using physical or laboratory tests, thus
making the diagnosis of CFS one of exclusion(DeLuca et al., 1997; Komaroff et al., 1997).
We report a patient with a rare association ofCFS and IgA nephropathy (IgAN).

Patient Report
In August 1994, a 43-year-old woman was referred to our hospital because of episodes ofproteinuria and occult hematuria. She was ahousewife and a sales representative of the department store. A renal biopsy done at this time
revealed IgAN to a moderate degree. Microscopic examination of her renal biopsy tissues
showed a focal segmental proliferative glomerulonephritis (Fig. 1). Mesangial granular deposits of IgA and C3 were identified by immunofluorescence.
During the follow-up where she was given a75 mg daily dose of dipyridamole she remained
Abbreviations: CDC, United States Centers for Disease Control and Prevention; CFS, chronic fatigue
syndrome; IgAN, IgA nephropathy; IU, International Unit

well, in a rather good condition, except for persistent microhematuria and proteinuria. In May
1995 she developed the sudden onset of profound fatigue, morning stiffness and low grade
fever without any clear precipitating factor.
Since that time, she has felt extraordinary weakness, finding herself unable to go to work. She
could not even go about household chores. The
exhaustion forces her to spend many hours inbed. Because of increasing severe myalgia andarthralgia, she was admitted to our hospital forthe second time in November 1996.
On admission, her weight was 62.8 kg andher height was 150.2 cm. Her lower extremities
were slightly edematous. Blood pressure was
150/72 mm Hg. Abnormal laboratory findings
were: urinary protein 2+, occult hematuria 2+,
urinary protein excertion 2.6 g/day, white blood
cell count 21700/µL, blood urea nitrogen 43
mg/dL, serum creatinine 2.0 mg/dL, uric acid9.7 mg/dL, total protein 5.0 g/dL, albumin 3.1g/dL and β2-microglobulin 2.85 mg/L. Serological tests for rheumatoid factor, antinuclear
and antineutrophil cytoplasmic antibodies, hepatitis B and C, Epstein-Barr virus and herpes simplex
virus were negative. Serum IgA 188 mg/dL, acylcarnitine 15.4 µmol/L, creatine phosphokinase
30 IU/L and C-reactive protein 0.01 mg/dL levels were within the normal range.

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K. KohamaFig. 1. Renal biopsy sample, periodic acid-Schiff-stained section (× 200).

All symptoms of the United States Centers
for Disease Control and Prevention (CDC) criteria except lymph node swelling were satisfied
in this patient. She complained of terrible muscle pain and multi-joint pain, even when she
turned over in bed. As a result of remarkablemuscle weakness, she could not go up stairs. At
the same time, atopic symptoms flared up on
her skin. A muscle biopsy on the biceps muscleof her arm was performed to exclude thepossibility of polymyositis or dermatomyositis(Fig. 2). But her biopsy tissues did not show
any abnormal findings.
Until now no controlled studies have provided convincing evidence of the efficacy of
any treatment for CFS. However, a recent report revealed that circulating levels of cortisol
in patients with CFS were relatively low(Mckenzie et al., 1998; Scott et al., 1998). To
evaluate the efficacy of oral hydrocortisone as atreatment for CFS, a 30 mg daily dose of prednisolone was initiated. Severe fatigue, myalgia
and fever were not improved. Then we tried
Chinese herbal medicine (Hochuekkito) and anonsteroidal anti-inflammatory drug (sulindac).
After administration of these drugs her myalgia,

arthralgia and even severe fatigue wereremarkably reduced. She was discharged inMay 1997.

Discussion
In 1988, the CDC proposed the term “chronicfatigue syndrome” and a definition for diagnosis. This definition was refined in 1994 by theInternational CFS Study Group (Nishikai,1996). The revised CFS classification criteria
requiresa) severe fatigue persisting for more than 6months,b) chronic fatigue of a new or definite onset,
not the result of ongoing exertion, not substantially relieved by rest and resulting in a
substantial reduction in previous levels ofsocial or personal activities,c) four or more of the following symptoms occurring concurrently: impairment of memory or concentration, sore throat, tender cervical or axillary lymph nodes, muscle pain,
headache, unrefreshing sleep and postexertional malaise.

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CFS and IgAN occurring in the same patient

Fig. 2. Muscle biopsy sample (× 200).

This report is the first description of CFS
associated with IgAN. Because immunemediated mechanisms may be a cause of IgAN
and CFS, we hypothesized that this association
might be linked with a common pathogenesis.
IgAN is the most common form of glomerulonephritis, with a prevalence ranging from
10% of renal biopsies in the United States to
30–40% in Japan (Hemmen et al., 1997). The
mean age range is generally in the second or
third decade. Haematuria as the presenting
symptom is found in 80% and proteinuria in
71% of the patients. In 40% of the patients withIgAN, the progressive disease leads to endstage renal failure. Recently, the role of themonocyte system and IL6 secretion in thepathogenesis and progression of IgAN has beenemphasized (Tsimaratos et al., 1996). It has beensuggested that age-dependent variations in thedevelopment of the IgAN mucosal system or individual differences in antigen exposure or
handling of immune complexes may play animportant role. The prevalence of DQ4/8/9 andDR4 is high among Japanese patients withIgAN (Taniguchi et al., 1997).

Immunologic abnormalities are also reported in CFS (Plioplys et al., 1997): decreased
function in natural killer cells and macrophages; reduced mitogenic response of lymphocytes; B-cell subset changes, and activation ofCD8 cells. There have also been reports of thepresence of circulating immune complexes, decreased complement, and the presence of anticardiolipin and antiphospholipid antibodies.
However, the evidence for an immunologicalbasis for CFS is as tantalizingly non-specific asis the evidence for a viral etiology (Dickinson,1997).
The present patient may provide further
immune-mediated mechanisms for IgAN andCFS.

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K. Kohama

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(Received December 22, 1998, Accepted February 2, 1999)

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