Infliximab infusions for persistent back pain in two patients with ...

1588 Letters to the Editor
6. LaSpina M, Russo G. Pneumococcal sepsis in a girl with systemic
lupus erythematosus. Br J Haematol 2003;122:172.
7. Kang I, Park SH. Infectious complications in SLE after
immunosuppressive therapies. Curr Opin Rheumatol 2003;5:528–34.
8. Pettersson T, Julkunen H. Asplenia in a patient with systemic
lupus erythematosus and antiphospholipid antibodies. J Rheumatol
1992;19:1159.
9. Obarski TP, Stoller JK, Weinstein C, Hayden S. Splenic infarction.
A new thrombotic manifestation of the circulating lupus anticoagulant.
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Rheumatology 2005;44:1588
doi:10.1093/rheumatology/kei144
Advance Access publication 18 October 2005
Functional asplenia in a patient with Rothmann–Makai
syndrome: a pathogenetic relationship?
SIR, A 27-yr-old woman was referred for evaluation of mild
anaemia, leucocytosis and thrombocytosis. History revealed a
diagnosis of Rothmann–Makai syndrome (lipogranulomatosis
subcutanea), a rare variant of Weber–Christian disease, at the
age of 13 yr. At that time the patient had presented with a minor
fracture of the left ankle, and when the plaster was removed she
was found to have irregular red discoloration on the outer part of
the ankle. This subsequently spread to involve both shins. A biopsy
specimen was obtained from one of the erythematous nodules.
In the histopathological sections there was a moderate lymphocytic
infiltration in the lobules of the panniculus and fibrocytes invading
the lobules from the fibrous septae. Work-up at that time also
included antinuclear antibodies (ANA), rheumatoid factor (RF),
C-reactive protein (CRP), anti-double-stranded DNA, anticardiolipin,
anti-Scl-70 and cryoglobulins, which were all negative.
A complete blood count was normal. With these findings and
lack of any systemic manifestations, a diagnosis of Rothmann–
Makai syndrome was established. The patient received an 8-month
course of steroids. The erythema resolved and the patient was
left with two slightly atrophic areas in both calves. No relapse has
occurred. History also revealed Hashimoto’s thyroiditis diagnosed
at the age of 14 yr and the onset of alopecia areata at the age
of 20 yr.
The patient has developed progressive increase in her leucocyte
count [(8–12) 10 9 /l] with a normal distribution and platelet count
[(450–600) 10 9 /l] over the past 8 yr. When seen in our clinic
she was feeling well. Except for obesity, the physical examination
was unremarkable. Haemoglobin was 14 g/dl with normal red
cell indices, the platelet count was 668 10 9 /l and the leucocyte
count was 16.2 10 9 /l with a normal distribution. A peripheral
blood smear revealed anisopoikilocytosis and numerous
Howell–Jolly bodies, indicating functional hyposplenism.
Computed tomography revealed a small spleen and no flow signals
could be derived by colour Doppler measurements from the spleen.
Rothmann–Makai syndrome is a rare form of Weber–Christian
disease, usually seen in adolescent and middle-aged women [1].
Subcutaneous nodules develop during the course of the disease
whereas systemic manifestations are absent. Multiple painless
nodules appear throughout the muscle and subcutaneous tissues.
The primary pathological process is lobular panniculitis, which
passes through the same three stages as Weber–Christian disease.
In the first stage, there is acute inflammation of the fat lobules with
fat cell degeneration accompanied by an infiltrate of neutrophils,
lymphocytes and macrophages. The second stage is characterized
by many foamy histiocytes, and the infiltrate is discretely
localized to the fat lobules. Finally, the foam cells are replaced
by fibroblasts. The first two histological stages correspond to
clinically apparent induration, while in the third stage atrophy of
the skin may develop. There are no diagnostic laboratory findings.
The diagnosis is based upon clinical and pathological findings.
Corticosteroid treatment does not prevent new lesions or seem to
alter the course of the self-limited disease.
Infiltrative, inflammatory or thromboembolic processes in the
parenchyma of the spleen can cause a functional loss of the organ.
This phenomenon is called functional asplenia and occurs as a
complication, especially in sickle cell disease, lupus erythematosus
(SLE) and after bone marrow transplantation [2–4]. Functional
asplenia has complicated the course of autoimmune diseases other
than SLE, such as candidiasis endocrinopathy syndrome and
alopecia areata [5].
This is the first report of functional asplenia occurring in
the setting of Rothmann–Makai syndrome. The aetiology and
pathogenesis of Rothmann–Makai syndrome is still unknown.
Christian–Weber disease often occurs in patients with autoimmune
disorders [6–8], as is the case with our patient, reinforcing the view
that Rothmann–Makai syndrome, a variant of Christian–Weber,
may also have an autoimmune basis.
The authors have declared no conflict of interest.
A. PSYRRI and T. ECONOMOPOULOS
2nd Department of Internal Medicine, Attikon University
Hospital, Athens, Greece
Accepted 2 September 2005
Correspondence to: A. Psyrri, Attikon Hospital, Rimini 1,
Haidari, Athens, Greece. E-mail: Diamando.Psyrri@yale.edu
1. Bondi EE, Margolis DJ, Lazarus GS. Panniculitis. In: Freedberg IM,
Eisen AZ, Wolff K et al., ed. Fitzpatrick’s Dermatology in General
Medicine, 4th edn. New York: McGraw-Hill, 1999:1275–89.
2. Santilli D, Govoni M, Prandini N, Rizzo N, Trotta F.
Autosplenectomy and antiphospholipid antibodies in systemic
lupus erythematosus: a pathogenetic relationship? Semin Arthritis
Rheum 2003;33:125–33.
3. Wong WY. Prevention and management of infection in children with
sickle cell anaemia. Paediatr Drugs 2001;3:793–801.
4. Kalhs P, Panzer S, Kletter K et al. Functional asplenia after bone
marrow transplantation. A late complication related to extensive
chronic graft-versus-host disease. Ann Intern Med 1988;109:461–4.
5. Boni R, Trueb RM, Wuthrich B. Alopecia areata in a patient with
candidiasis-endocrinopathy syndrome: unsuccessful treatment trial
with diphenylcyclopropenone. Dermatology 1995;191:68–71.
6. Billings JK, Milgraum SS, Gupta AK, Headington JT,
Rasmussen JE. Lipoatrophic panniculitis: a possible autoimmune
inflammatory disease of fat. Report of three cases. Arch Dermatol
1987;123:1662–6.
7. Yoshimura A, Itoyama S, Mori S, Mori W, Inoue G. An autopsy
case of Weber-Christian with immune complex glomerulonephritis.
Nippon Jinzo Gakkai Shi 1988;30:291–6.
8. Herr W, Lohse AW, Spahn TW et al. Nodular nonsuppurative
panniculitis in association with primary biliary cirrhosis and
Hashimoto’s thyroiditis. Z Rheumatol 1996;55:122–6.
Rheumatology 2005;44:1588–1590
doi:10.1093/rheumatology/kei155
Advance Access publication 18 October 2005
Infliximab infusions for persistent back pain
in two patients with Schmorl’s nodes
SIR, Schmorl’s nodes (SNs) are herniations of the nucleus
pulposus (NP) material through the vertebral endplates into the
trabecular bone. SNs are the most common non-intervertebral disc
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FIG. 1. Post-contrast T1-weighted image of lumbar spine in the
first patient prior to (A) and 6 months after (B) infliximab
infusions, showing disappearance of enhancement of Schmorl’s
node and of oedema of adjacent vertebral body marrow.
abnormalities in magnetic resonance imaging (MRI) in persons
without back pain [1]. However, SNs are seldom symptomatic, and
treatment with analgesics, non-steroidal anti-inflammatory
drugs (NSAIDs) or corticosteroids usually improves back pain.
In contrast to SNs, herniated intervertebral discs (HIDs) are a
common cause of back and radicular pain. TNF- from the NP
does appear to be pathogenic to nerve roots in animal models
of sciatica [2]. Furthermore, TNF- blockade is effective in
preventing NP-induced functional and structural nerve root injury
in animal models [3]. The efficacy of the TNF- inhibitors
infliximab and etanercept in leg and back pain has recently been
shown in patients with HID-induced sciatica [4, 5]. These results
of TNF- blockade prompted us to test infliximab infusions
for refractory symptoms to conventional conservative treatment in
two patients with painful SN.
Two women aged 52 and 49 yr with SNs received infliximab
because of severe, long-standing back pain (duration of pain 24
and 18 months, respectively) without radicular symptoms. There
was a partial response of pain to treatment with NSAIDs and
corticosteroids in both patients, but severe spinal pain recurred
after discontinuation of the above agents. SNs of the L3 and L5
vertebrae in the first patient and of the T12, L1 and L2 vertebrae
in the second patient were depicted by MRI. There were MRI
findings of active SN (oedema of adjacent bone marrow and
contrast enhancement of SN) in the L5 vertebra for the first patient
and in the L2 vertebra for the second patient. After obtaining
ethics committee approval and written consent from the patients,
the patients scheduled to receive infliximab infusions at a dose
of 3 mg/kg at weeks 0, 2, 6 and 14. Response was evaluated
using a 0–100 mm visual analogue scale (VAS) for back pain.
Furthermore, the first patient was evaluated for radiological
progression of the lesions by sequential MRI examination.
Prior to infliximab treatment, the VAS score for back pain for
the two patients was 90 and 85, respectively. The first patient
responded promptly to infliximab with a decrease in VAS for back
pain to 7, and back pain completely resolved after the second
infusion. Due to a severe allergic reaction just after the second
infusion, she discontinued the infliximab regimen. Six months
later, MRI examination revealed disappearance of contrast
enhancement of SN of the L5 vertebra and of bone marrow
oedema (Fig. 1). She has remained asymptomatic for 30 months.
Letters to the Editor 1589
The second patient completed four infliximab infusions. She
also responded promptly to treatment. VAS for back pain ranged
from 15 to 20 at weeks 2, 6 and 14. She was missed 5 months
after the last infliximab infusion, and had VAS for back pain 20
over the follow-up period.
MRI is useful in differentiating between symptomatic and
asymptomatic SNs. In an analysis of MRI findings of SNs [6],
the vertebral body marrow surrounding the SN was seen as low
signal intensity on T1-weighted images and as high signal intensity
on T2-weighted images in all symptomatic cases. These MRI
findings were not seen in asymptomatic individuals. Histological
examination of two symptomatic cases demonstrated bone
marrow oedema and inflammatory cell infiltration in the affected
vertebral body. In a small number of cases of acute SNs [7], there
had been improvement in back pain by the time the follow-up
MRI (between 6 weeks and 7 months after the initial MRI)
showed reduction in bone marrow oedema. Furthermore, there
was resolution of oedema with fatty marrow change in two
cases with longer follow-up at MRI (10 and 18 months after
the initial MRI, respectively). In addition to surrounding bone
marrow oedema, MRI can reveal vascularized tissue in SNs
after the intravenous administration of contrast material [8].
Contrast-enhancing SNs are larger and more frequently associated
with bone marrow oedema in patients with back pain than in
asymptomatic patients.
Our patients had not only severe back pain, which was induced
by active SNs (L5 vertebra in the first patient and L2 vertebra in
the second patient), but also long-standing symptoms, which
could be explained by previous active SNs that were in the healing
stage at the time of MRI examination (L3 vertebra in the first
patient and T12 and L1 vertebra in the second patient). A single
infliximab infusion for HID-induced sciatica produced not only a
sustained but also an immediate improvement (within hours) [4].
The first infliximab infusion led to prompt and significant
improvement in back pain in our patients within the first 24 h.
There was a complete response to the second infliximab infusion
in the first patient, but the second patient did not have a
complete improvement of back pain with the four-dose infliximab
regimen. A pilot study is required to validate the results of our two
case reports.
Rheumatology
Key message
TNF- blockade seems to be effective for
persistently painful Schmorl’s nodes.
The authors have declared no conflicts of interest.
G. T. SAKELLARIOU, I.CHATZIGIANNIS and I. TSITOURIDIS 1
Department of Rheumatology, St Paul’s Hospital and
1
Department of Radiology, Papageorgiou Hospital,
Thessaloniki, Greece
Accepted 9 September 2005
Correspondence to: G. T. Sakellariou, Department of
Rheumatology, St Paul’s Hospital, 161 Ethnikis Andistaseos
Street, 551 34, Thessaloniki, Greece. E-mail: sakelgr@otenet.gr
or sakellariou.doc@mycosmos.gr
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1590 Letters to the Editor
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