Dercum¥s disease - a frequently overlooked
disease picture:
J. Steiner, K. Schiltz, F. Heidenreich, K. Weissenborn (2002) NERVENARZT 73: 183-187
Neurologische Klinik, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1,
30625
Neurologische Klinik II,
Otto-von-Guericke Universit”t
Abstract
Dercum's disease (lipomatosis dolorosa) is a relatively unknown illness.
The disorder usually affects middle-aged females. Subcutaneous fatty tissue
deposits may occur in many parts of the body. The upper arms, elbows, stomach
wall, buttocks, thighs, or knees are most commonly affected. Severe hyperalgesia is found on light pressure and touch.
Analgesics or pain-modulating drugs usually have little or no effect. The
following case report demonstrates successful symptomatic treatment of the
otherwise nearly unbearable complaints: intravenous infusions of 5 mg/kg body
weight of lidocaine over 30ñ90 min may give pain relief lasting several weeks
or even months. Alternatively, patients are treated with 150ñ750 mg orally
administered mexiletine daily. Surgical excision or liposuction of these fatty tissue deposits have shown
significant reduction of pain. However, this effect reduces over time and
recurrences often develop.
___________________________________________________________________________
Dercum's disease (lipomatosis dolorosa)
is a relatively unknown illness, although it was first described by the
American neurologist Francis Xavier Dercum (1856 ñ 1931)
in 1888 [9, 10]. A number of synonyms can be found in the medical specialty
literature, including adiposalgia, adiposis dolorosa, adipositas
dolorosa, Dercum's disease, adipose tissue rheumatism
(
Because of the painful subcutaneous fat deposits associated
with the syndrome, this substantially dermatological pathology is of relevance
to neurologists and pain therapists. The symptoms are virtually unaffected by
conventional analgesics or classical pain modulation therapy (e.g.
amitriptyline, carbamazepine). A better understanding of the characteristic
syndrome would assist in early diagnosis and avoidance of unnecessary treatment
attempts. The purpose of this article is, therefore, to introduce the current
state of knowledge and opportunities for promising pain therapy.
Case report
A 47 year old female patient noticed for the first time in
the late 80s multiple nodules on the inner surface of both upper arms; later 2
deep nodules on the left inner thigh were also noticed. When, in 1990 pain on
contact and pressure occurred at the skin changes, the patient presented at a
general practitioner, who informed her that it were lipomas ñ lipomas, however, do not cause pain.
Nevertheless, the
stress of the discomfort resulted in removal of 15 of these tumors in 1992. The
histology of these tumors was characteristic of lipoma
and in part also angiolipoma. In the ensuing years lipomas recurred, predominantly on the inner surface of the
upper arm and in the proximity of the elbow joint (Fig. 1), which were again
tender and sensitive to pressure. The symptoms were aggravated in winter and at
emotional stress. The patient intermittently complained of tingling paresthesia
at the fingertips accompanied by grip impairment. In addition, there was a
predisposition to ecchymoses. Since the patient complained of occasional
swelling of the fingers and dryness of the mouth lasting for days, provisional
pain therapy with meloxicam (MobecÆ)
was instituted on the presumption of rheumatoid disease. The medication was
later changed to tramadol (TramalÆ). However, neither
of the two medications was effective. In 1998 pain had reached such a level
that it interfered with the patient's sleep and she could no longer rest the
arms on the torso. It was at this time that the patient presented in our
department for the first time; initially on the presumption of a
neurofibromatosis. The neurological examination was unremarkable except for a
painful limitation of movement in both arms. CafÈ-au-lait
spots were not observed and the cranial and cervical MRI studies were
unremarkable ñ in particular, neurofibromas
were not demonstrated. At laboratory testing all routine parameters were within
normal, ESR 16 / 42 normal; RF, ANA, cANCA
and pANCA were negative. A Raynaud
phenomenon with typical cold-induced discoloration of the distal parts of the
extremities (tricolor phenomenon) was excluded in the differential diagnosis. Electroneurography also did not provide evidence of the
presence of a sulcus-ulnaris or a carpal tunnel
syndrome. Based on the characteristic constellation of findings, we made the
diagnosis of Dercum¥s disease.
In November 1998, January 2000, July 2000, October 2000 and
May 2001 systemic doses of lidocaine were administered. Initially, a test dose
of 100 mg of lidocaine was administered i.v. over
2 ñ 3 minutes. Thereafter, at each cycle of therapy for a total of 4
days, the dose of 300 mg lidocaine was administered over 90 minutes. After the
2nd infusion, the patient was consistently pain-free. After 3 ñ 6
months the symptoms gradually reappeared but not in the severe intensity as
prior to the start of lidocaine therapy. Save for a slight drop in blood
pressure and a sensation of warmth in the whole body, there were no adverse
reactions.
Discussion and review
The diagnosis of Dercum¥s disease is made clinically, but histopathological examinations should be undertaken ñ
especially to rule out malignancy. Characteristically, painful subcutaneous
adipose tissue deposits occur in overweight females (Rubens figure) in middle
age. The patient treated by us was also overweight (80 kg, 158 cm). The
syndrome is 5 ñ 30 times more frequent in women than in men. The
majority of cases occur sporadically, as in the case presented. Only 3
publications describe a familial cluster based on autosomally
dominant inheritance with incomplete penetration [4, 5, 18].
There is no reliable information on prevalence, since the pathogenesis is not
completely understood. Brorson and Fagher, however, estimate that in
Tender and pressure-sensitive adipose tissue occurs
particularly at various sites of predilection: the inner surface of the upper
arm and elbow joint, abdomen, buttocks, the inner and outer surface of the
thigh and knee joint (Fig. 2). As a rule, the face and the hands are spared.
Usually the pain symptoms increase insidiously over months to years. Slight
pressure, touch, closely fitting clothing or water when showering can be
perceived as unpleasant. The pain is dependent on weather conditions and
improves as a rule in dry heat. Our patient reported that the symptoms
temporarily abated after a hot bath. According to the pain distribution pattern,
the following sub-typing can be done [3]:
Type I (juxta-articular):
painful fatty tumors at the inner surface of the knee, on the hips, less
frequently at the elbow joint.
Type II
(diffuse ñ generalized): diffuse
tenderness on the dorsal surface of the upper arm, axillar,
gluteal, on the abdomen, back and on the soles of the
feet; abdominal pain can frequently predominate.
Type III
(nodular): particularly lipomas painful on pressure; frequently also in the absence
of overweight. Several of these lipomas
were ñ as in the present case ñ histologically
classified as angiolipomas, because they exhibited a
pronounced density of blood vessels.
Dercum¥s disease causes a number of psychosocial problems. The
chronic hyperalgesia frequently impairs sexual
relations or results in occupational invalidity. Emotional changes were
repeatedly described in the literature such as, for example, irritability,
depression, fatigue, lack of drive, sleep or memory
disorders. These symptoms can also be interpreted as psychoreactive
concomitant symptoms in the context of chronic pain symptoms (see the case
reports of the American Self-help Group, Dercum's
Support: http://www.dercum.org). Many of
our patient's symptoms described in the casuistics
are typical accompanying symptoms of Dercum¥s disease
[3].
Swelling of the hands and fingers with
accompanying paresthesias, numbness or carpal tunnel syndrome. Joint stiffness after rest, particularly
in the morning. Dryness of the eyes and mouth. Telangiectasia with increased fragility of the dilated
vessels; accordingly a tendency to bluish-red discoloration and ecchymoses;
there is no disorder of coagulation. Headache (tension
headache, migraine, cervicogenic headache).
Differential diagnoses
Other diseases coexist with Dercum¥s
disease, which result in a disorder of adipose tissue distribution and must
therefore be considered in the differential diagnosis. For example, in benign
symmetrical lipomatosis, adipose tissue pads occur,
which in contrast with Dercum¥s disease are not
painful. The predominance is in middle-aged men. Fat accumulation in the area
of the upper mediastinum can result in compression of
the respiratory passages. According to Donhauser et
al. [13] three types can be differentiated according to the localization of the
fatty pads:
I. Madelungís-disease [adenolipomatosis syndrome] or cervico-nuchal
type;
II. Shoulder-girdle or pseudoathletic
type:
III. Pelvic-girdle or gynecoid
type.
An alcohol-abuse or hepatopathological
etiology is assumed. Lipedema, in contrast, occurs in
women with a genetically determined disorder of fat distribution. The
underlying lipohypertrophy, wherein the extremities
are thickened symmetrically with the trunk, predominantly affects the legs and
is initially painless. Edema occurs in the course of lymphostasis
due to the pressure of increased fat cells on small lymph vessels. Symptoms in
the form of a feeling of heaviness, tension pain and pressure sensitivity or
tenderness then occur. A collar-like termination of the edema over the ankle or
wrist joint is typical [15].
Only in recent years has it become known that disorders of
fat distribution can occur also in HIV patients in the context of retroviral
therapy with protease inhibitors. This so-called HIV lipodistrophy
is accompanied by atrophy of the adipose tissue in the face, extremities and
buttocks. In contrast, there is an increase in adipose tissue on the trunk (truncal obesity) and neck (steer neck). A Cushing's habitus, which is frequently
associated with metabolic disorders like hyperlipidemia,
hypercholesterolemia and diabetes mellitus. As a rule, pain does not occur;
however, cases with painful angiolipoma have been
described [7].
Pathogenesis
The underlying pathogenetic
mechanisms continue to be unknown. Furthermore, there are no systematic studies
of larger numbers of cases and many Soviet and Swedish publications are
difficult to access for western medicine.
Disorders of lipid metabolism or endocrine disorders are
presumed to be the cause of the disease: Blomstrand
et al. found a disorder of C18 fatty acids in two cases [2]. Fagher et al., however, arrived at a different conclusion
in a study of 13 patients and found enlarged adipocytes
at histological examination in comparison with controls of identical weights
[14]. Histological studies have so far produced heterogeneous findings, wherein
principally unremarkable adipose tissue was demonstrated. In 1888, Dercum found evidence of neuritis; this finding has,
however, remained unconfirmed [9]. Until the mid 20th Century, the skin changes
in lipomatosis were presumed to be in relation with myxedema. This was based on the frequently observed
association of the pathologies with thyroid gland dysfunction, in particular
hypothyroidism. When, however, in the 50s a female patient was treated with a
thyroid hormone preparation and died, this hypothesis was abandoned [22]. Also
in our patient, a subtotal resection of the thyroid was done in 1991 due to a
nodular goiter and thereafter thyroxin was substituted. However, there was no hypothyrosis. It is theorized that subcutaneous adipose
tissue deposits cause the pain symptoms by compression of the nerves. Skagen et al. demonstrated perturbations of subcutaneous
blood flow in one female patient. Remission of pain and normalization of the
subcutaneous blood flow for one month was achieved by systemic lidocaine
administration. Based on this observation, the authors concluded an association
of the sensitivity of the adipose tissue with a sympathetic dysregulation
[21]. It is unclear, whether and if indeed, what role the increased blood
vessel density of the angiolipoma plays in comparison
with the lipomas. In a systematic study of 50 angiolipomas, Dixon et al. nevertheless found no connection
between the extent of vascularization and pain
intensity [12].
Therapy
Treatment of the Dercum¥s disease
has the primary goal of achieving relief from pain. Surgical excision or
liposuction, for example of juxta-articular adipose
tissue accumulations, can provide temporary pain relief. The effect diminishes
over time and recurrences often occur [3]. We would therefore recommend
surgical removal only of individual, particularly painful lipomas.
Weight reduction appears not to have an affect on the pain symptomology
and conventional analgesics have, as already mentioned,
little effect.
Intravenous administration of lidocaine, on the other hand,
provides in many patients weeks to months of complete freedom from pain.
Accordingly, in the majority of publications, per treatment cycle single-dose
approximately 5 mg / kg body weight of lidocaine is administered over
30 ñ 90 minutes [1, 11, 16, 20, 21]; in a case description, however,
approximately 15 mg of lidocaine / kg body weight was administered i.v. on 4 ñ5 consecutive days, in order to achieve
durable freedom from pain [17].
Systemic lidocaine administration has been used in pain
therapy for some 40 years, especially in difficult to treat neuropathic pain.
On the other hand, local administration of lidocaine is generally without
effect. Alternatively or supplementally,
the local anesthetic mexiletine, which can also be
administered in tablet form. has been used
successfully. Accordingly, dosages of 150 ñ 170 mg daily are
administered [6, 8, 11, 20]. After consultation with
the cardiology department of Medizinische Hochschule Hannover, no effort
was made for intermediate treatment of our patient with mexiletine,
since cardiovascular adverse effects must be taken into account. In view of the
comparatively long persistence of the lidocaine effect in our patient, this
risk was not justified. Prior to systemic lidocaine therapy, 2nd and 3rd degree
AV block or sick sinus syndrome must be ruled out as contraindications.
According to publications to date, tolerability of the treatment is generally
good. During infusion, however, continuous ECG and RR monitoring should be
done, because cardiovascular adverse effects must be taken into account. A fall
in blood pressure, arrhythmias, bradycardia and, in
very rare cases, asystole can occur. In addition,
slight central nervous system side effects such as vertigo, dizziness or
paresthesias can frequently occur. Many patients report slight headache or
nausea after infusion. Furthermore, disorientation, vision and speech
disturbances, tinnitus and tremor have been observed. Very rarely, reduction in
vigilance, respiratory depression or epileptic events can occur.
The same contraindications apply to treatment with mexiletine and similar cardiovascular and central nervous
system adverse events can occur. In addition, there are frequently
gastrointestinal symptoms such as, for example, heartburn, abdominal pain,
nausea and vomiting. Rare adverse effects are: skin reactions including
Stevens-Johnson-syndrome, liver damage, pulmonary fibrosis, leukocytopenia
or thrombocytopenia. In outpatient mexiletine
treatment, therefore, weekly ECG and monthly prolonged ECG, as well and blood
testing and liver values must be done.
Interestingly, the duration of the effect of lidocaine
infusions (10 h to 12 months) is generally appreciably longer than one would
have assumed based on the biological half-life (first 30 minutes after i.v. administration: half-life 7-10 min by tissue
distribution; thereafter half-life 90 ñ 120 min by metabolism and
excretion). The underlying mechanisms of activity are still incompletely
understood. Animal experimental studies allow the hypothesis that an increased
density of voltage-dependent sodium channels in damaged axons and in the
associated spinal ganglia result in spontaneous ectopic
discharges and thus to neuropathic pain. Electrophysiological studies show that
by systemic lidocaine administration, these spontaneous discharges can be
suppressed without blocking normal nerve conduction.
According to more recent studies, there are more than 10
different sodium channels that are responsible for the production and
propagation of an action potential. Especially the sub-group of tetrodotoxin resistant sodium channels appears to play a
special role in pain modulation. In peripheral nerve lesions down-regulation of
the tetrodotoxin-resistant sodium flux and an
up-regulation of the tetrodotoxin-sensitive sodium
flux was demonstrated. Lidocaine acts approximately 4 times more potently on tetrodotoxin-sensitive sodium channels and was thus capable
of correcting the imbalance of the sodium fluxes in neuropathic pain.
Summary
Pain in the area of the subcutaneous adipose tissue
deposits is characteristic of the clinical picture of Dercum¥s
disease. Women in middle age are particularly affected by the disease.
Unfortunately, the underlying pathogenetic mechanisms
continue to be unknown. However, it is assumed that nociceptors
and afferent axons are damaged by the local compression by the adipose tissue
deposits. In addition, a sympathetic dysregulation
and perturbation of the subcutaneous blood flow appears to be of significance.
Chronic pain (persisting longer than 3 months) occurs and appears spontaneously
or can be provoked by light contact stimuli (allodynia).
Cold external temperatures also trigger the occurrence of the pain described as
burning, cutting or stabbing. The symptoms are hardly affected by conventional
analgesics or classical pain modulating therapy. Based on the stated features,
we consider the assignment of the disease to the neuropathic pain syndromes as
justified. Dercum¥s disease appears to respond
satisfactorily to systemic lidocaine or mexiletine
administration. This therapy has been shown in the past to be effective in
numerous other neuropathic pain syndromes.
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