Rheumatology 2005;44:1322–1333
Letters to the Editor
Rheumatology 2005;44:1322–1323
doi:10.1093/rheumatology/kei026
Advance Access publication 16 August 2005
(Total IgG, %)
P<0.005
40
Beneficial effects of steroid therapy for Mikulicz’s disease
SIR, Mikulicz’s disease (MD) represents a unique condition
involving symmetrical enlargement of the lacrimal and salivary
glands, the cause of which is unknown. It has been included within
the diagnostic criteria for primary Sjögren’s syndrome (SS) due to
their histological resemblance [1]. However, it is clear that the
pathogenesis of MD differs from that of SS because an elevated
serum IgG4 concentration and infiltration of abundant plasmacytes with IgG4 into the lacrimal and salivary glands are seen
in MD patients [2]. Clinically, MD exhibits good responsiveness
to glucocorticoids, showing improvements in not only lacrimal
and salivary gland swelling but also secretion. We attempted to
objectively document this phenomenon and to serologically
evaluate steroid efficacy.
Analyses were performed in eight MD patients (two men, six
women) who consulted doctors at Sapporo Medical University
between April 1997 and January 2005. MD was diagnosed
according to the following criteria: (i) persistent (more than
3 months) symmetrical swelling of more than two lacrimal and
major salivary glands; (ii) prominent mononuclear infiltration of
lacrimal and salivary glands; and (iii) exclusion of other diseases
that exhibit glandular swelling, such as sarcoidosis or lymphoproliferative disease [2]. Lacrimal gland function was evaluated by
Schirmer’s test, and salivary gland function was examined by
Saxon’s test. IgG subclass was measured by nephelometry. These
tests were performed before and after treatment. Mann–Whitney’s
U-test was used for data comparison, and values of P<0.05 were
considered statistically significant.
After prescription of 30–40 mg prednisolone/day, lacrimal
secretion increased from 6.90±0.77 to 15.70±11.56 mm/5 min
(P<0.05), and salivary secretion improved from 1.98±1.86 to
3.66±0.77 g/2 min after treatment (P<0.05). Serum IgG concentration decreased from 4270.0±2098.0 to 1440.1±424.7 mg/dl
(P<0.005). Serum levels of each IgG subclass decreased as follows:
IgG1, from 1632.9±781.1 to 681.0±227.5 mg/dl (P<0.005);
IgG4, from 1556.4±937.1 to 234.7±75.3 mg/dl (P<0.005). IgG
subclass/total IgG ratio also changed, as follows: IgG1, from
38.26±3.92 to 46.83±3.98% (P<0.01); IgG4, from 34.85±7.87
to 16.67±5.88% (P<0.005) (Fig. 1).
Glucocorticoids have long been known to effectively improve
lacrimal and salivary gland swelling in MD. However, we noted
that sicca symptoms were improved when we followed MD
patients being treated with steroids. The present results confirmed
a tendency for improvement in lacrimal and salivary secretion 2–3
months from the start of steroid treatment in MD. On the other
hand, in SS, steroid therapy makes the lacrimal and salivary glands
smaller, but is not able to improve gland secretion. SS is an
autoimmune disease that mainly destroys glands. We initially
hypothesized that steroids are not effective in SS because it is
diagnosed after some degree of progression, while steroids are
effective in MD because it is diagnosed earlier (onset of changes in
facial appearance). However, our MD cases suffered from dryness
for several years, and yet gland function improved after glucocorticoid administration. Tsubota reported fewer apoptotic cells
in the lacrimal glands in MD when compared with SS [3], and
we observed this phenomenon in salivary glands in MD [4].
The low number of apoptotic cells is thought to be related to the
reversibility of gland secretion in MD.
30
20
10
0
IgG1 IgG2 IgG3 IgG4
Pre-Tx.
IgG1 IgG2 IgG3 IgG4
Post-Tx.
(n =8)
(After 4.8 months)
FIG. 1. Changes in the ratio of each serum IgG subclass to
total IgG after steroid therapy in Mikulicz’s disease. Ratio of
serum IgG4 was significantly decreased after corticosteroid
administration.
The present analysis proves that different approaches to
secretory function are necessary for MD and SS. In SS, cevimeline
hydrochloride stimulates the remaining gland function and
promotes secretion; however, active steroid treatment is of
particular value in MD because glandular destruction has not
occurred.
One of the serological characteristics of MD is an elevated
concentration of IgG4. In addition, the ratio of serum IgG4 to
total IgG is 34.85%, while in healthy controls the ratio is about
4%. It is known that the ratio does not vary with race, sex or age
after adulthood. We found that the serum IgG4/total IgG ratio
decreased significantly in MD patients after steroid therapy,
although it is expected that steroids would decrease IgG4
concentration as a result of immune suppression. This phenomenon may be related to disease activity and the subsequent
improvement in symptoms. However, in our MD cases the serum
IgG4/total IgG ratio failed to normalize, and increased after
tapering or interrupting the steroid dose (<5 mg prednisolone/
day). We believe that 5–7.5 mg prednisolone/day is necessary to
maintain disease suppression.
The authors have declared no conflicts of interest.
M. YAMAMOTO, S. HARADA, M. OHARA, C. SUZUKI, Y. NAISHIRO,
H. YAMAMOTO, H. TAKAHASHI, Y. SHINOMURA, K. IMAI1
First Department of Internal Medicine, Sapporo Medical
University, School of Medicine and 1Sapporo Medical
University, Sapporo, Hokkaido, Japan
Accepted 10 June 2005
Correspondence to: M. Yamamoto, First Department of
Internal Medicine, Sapporo Medical University, School of
Medicine, South 1-West 16, Chuo-ku, Sapporo, Hokkaido,
Japan. E-mail: [email protected]
1. Morgan WS, Castleman B. A clinicopathologic study of Mikulicz’s
disease. Am J Pathol 1953;29:471–503.
2. Yamamoto M, Harada S, Ohara M et al. Clinical and pathological
differences between Mikulicz’s disease and Sjögren’s syndrome.
Rheumatology 2005;44:227–34.
The Author 2005. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: [email protected]
Letters to the Editor
3. Tsubota K, Fujita H, Tsuzaka K, Takeuchi T. Mikulicz’s
disease and Sjögren’s syndrome. Invest Ophthalmol Vis Sci
2000;41:1666–73.
4. Yamamoto M, Suzuki C, Naishiro Y et al. The study of differences
between Sjögren’s syndrome and Mikulicz’s disease in frequency of
apoptosis in salivary glands. Sugai S, ed. The 8th International
Symposium on Sjögrens syndrome, Kanazawa, Japan, pp. 45,
May 16–18, 2002.
Rheumatology 2005;44:1323
doi:10.1093/rheumatology/kei104
Advance Access publication 2 September 2005
Unifying abbreviations for biologicals
in trials and publications
SIR, The increasing use of biologicals in all kinds of rheumatological disorders and the rapid development and introduction of
novel drugs in this field has led to a variety of abbreviations
for each of the monoclonal antibodies and soluble receptors.
For example, when screening the literature of the past years, at
least seven different abbreviations or codes could be found for
infliximab, including INF, INFL, INX, IFN, IFX, IXM and IMB.
In contrast to the abbreviations that are generally accepted
nowadays for conventional DMARDs, such as MTX, AZA and
SSZ, this inhomogeneous coding for biologicals appears rather
confusing and does not support an easy understanding of figures
and tables addressing the outcome of biologicals-related research
and clinical trials. Therefore, it would be recommendable to
initiate a unifying abbreviation system that meets both the need for
practicability and logic as well as applicability for all present
and upcoming biologicals in rheumatology. For this purpose, the
following algorithm of a three-letter-coding system is suggested for
discussion.
The first two letters are the first two letters of the generic, i.e.
IN for infliximab, ET for etanercept, AD for adalimumab, etc.
The third letter indicates the biological structure or class of the
drug, i.e. X for a chimeric monoclonal antibody, Z for a humanized
monoclonal antibody, M for a human monoclonal antibody,
C for a soluble receptor/receptor–antibody fusion protein, and R
for a receptor antagonist. Table 1 shows the resulting codes for the
individual biologicals actually used in rheumatology.
1323
Rheumatology 2005;44:1323–1324
doi:10.1093/rheumatology/keh704
Advance Access publication 7 June 2005
Sacroiliitis presenting as sciatica
SIR, Sciatica is a common presentation but the underlying cause
may be sacroiliitis, which differs in prognosis and treatment
options. We present two cases of sacroiliitis presenting as sciatica.
The first case is a 28-yr-old man who for 18 months had recurrent
episodes of left buttock pain radiating down to the lower calf,
typical of sciatic pain. Straight leg raising and femoral nerve
stretch tests were negative and MRI of the lumbar spine showed
no evidence of disc herniation. MRI of the pelvis demonstrated
marked inflammation of the left sacroiliac joint. Symptoms
settled gradually with ibuprofen and conservative management.
He presented 15 months later with similar classical sciatica
symptoms, but this time on the right side. MRI revealed rightsided sacroiliitis and the previously involved left sacroiliac
joint was now normal (Fig. 1). Diagnosis of a reactive sacroiliitis
was made, and symptoms resolved with non-steroidal antiinflammatory (NSAID) therapy.
The second case is that of a 29-yr-old sports consultant
who presented with low back pain and classical sciatic pain
radiating into the left ankle, and a positive straight leg raising
test. X-rays revealed periarticular sclerosis of both sacroiliac
joints, with possible fusion on the left side. Further history
revealed low-grade psoriasis and iritis and a diagnosis of
psoriatic spondyloarthritis was made. Symptoms improved with
physiotherapy and valdecoxib.
Sacroiliitis causing symptoms of sciatica have been reported in
a handful of cases [1, 2]. But how can sacroiliitis cause symptoms
mimicking sciatica? Traditionally, sciatica was thought to be due
to mechanical nerve root compression caused by intervertebral
disc herniation. However, it is now evident that radicular pain is
not purely mechanical, and that nerve root inflammation and
subsequent nerve injury is important. In fact, up to 76% of people
without symptoms of back pain or sciatica have disc herniation
on MRI, and not all patients with sciatica have disc herniation on
MRI [3]. Inflammatory mediators, including pro-inflammatory
cytokines released from the nucleus pulposus, may contribute
U. MÜLLER-LADNER
University of Giessen, Kerckhoff Clinic, Bad Nauheim, Germany
Accepted 5 August 2005
TABLE 1. Basic abbreviation list for currently used biologicals in trials
and publications in rheumatology
Abbreviation/code
Biological/generic
ABC
ADM
ALC
ANR
EFZ
ETC
INX
ONC
RIX
TOZ
Abatacept
Adalimumab
Alefacept
Anakinra
Efalizumab
Etanercept
Infliximab
Onercept
Rituximab
Tocilizumab
FIG. 1. STIR angled coronal MRI demonstrating bone oedema
along the right sacroiliac joint in keeping with inflammatory
change, with normalized left sacroiliac joint.