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Lymphedema and Rheumatoid Arthritis

Case Reviews and Studies

In our online lymphedema support group Advocates for Lymphedema we recently had a discussion and many questions regarding the issue of lymphedema and rheumatoid arthritis.

Is it a chicken and egg situation wherein lymphedema causes RA or the reverse?

In presenting this page of case studies and reviews, the reader needs to know in advance that these studies are old, with one dating back to 1980. Unfortunately,There are no current studies available and no updated information is available.

If however, these studies are credible, then the prevailing evidence, from lymphograhpic imaging is that edema associated with rheumatoid arthritis results from lymphatic obstruction. This obstruction is caused by scarring of the lymphatics as a result of the inflammatory process involved with RA.

It is interesting also that there was mention in the last study presented that perhaps lymphedema from RA affects those who already have an “at risk” lymphatic system.

This also ties in with what Tom Kincheloe, a lymphedema therapist who is also a member of Advocates for Lymphedema, submitted in our discussion of this.

“In rheumatoid arthritis (RA), organic changes occur to the connective tissue channels and capillary lymph vessels (the smallest of the lymph vessels embedded within the connective tissues) around the synovial joints (the capsular components that contain the synovial fluid – our body's natural “WD-40”) due to chronic neurogenic inflammation. These connective tissue channels can become blocked by a clotting of fibrin, which is triggered by the inflammation, further blocking movement of lymph out of the interstitial tissues. The lymph vessels can also become infected (lymphangitis), which further impairs lymph movement. It appears, according to lymphography done by the authors, that cortisone injections into the inflammed joints might help with the inflammation but might also add to the blockage of fibrotic channels “due to particle suspensions” from the cortisone thus INCREASING the risk of lymphedema.

According to the researchers, “it is not surprising that rheumatoid arthritis can be accompanied by lympedema. There is a vicious circle in rheumatic inflammatory processes: pain –> neurogenic inflammation –> edema –> pain.”

Any of these conditions: bacteria, viruses, trauma, surgery, radiation, frostbite, burns, immune reactions, dead cells and cellular debris, shock, irritation of sensory nerve fibers (as in neurogenic inflammation), irregular shear stress, etc., can generate an acute inflammation response. In rheumatoid arthritis, it is chronic inflammation caused by “degranulation of the mast cells” that protect the sensitive nerve fibers resulting in chronic irritation and inflammation, which then leads to edema then lymphedema (if the inflammation is not controlled).

As I explained to the student nurses during my inservice a few days ago, edema is a symptom and lymphedema is a disease. Edema (swelling) will commonly occur with any type of injury or disease where any tissue is damaged (internally and/or externally) and is part of the normal initial inflammatory healing response. It's when it goes unresolved that the edema can develope into lymphedema because continuous inflammation and infection may destroy the tiny lymphatic vessels resulting in permanent damage to the lymphatic system.

So to answer your question: ANY inflammation response due to any of the above causes can lead to lymphedema, including RA.”

His reference book for this information was the Lymphedema textbook for Physicians and Therapists (Foldi and Foldi, eds.)

My deepest thanks to all who contributed to this discussion and who contributed information.

Pat

Lymphedema of the leg associated with rheumatoid arthritis

Vojnosanit Pregl. 1999 May-Jun

Article in Serbian] Ignjativić N, Cerović S.

Only a few cases of the occurrence of chronic lymphedema as a non-systemic, regional colagenosis associated with a real systemic disease of connective tissue, such as rheumatoid arthritis, have been reported so far. The aim of this article is to review an obridus case of chronic primary lymphoedema in a female patient suffering from rheumatoid arthritis. Reported lymphoedema appeared after many years of remission of rheumatoid arthritis and was not in correlation with its relapse. The doppler ultrasonography, lymphoscintigraphy and histopathological examination confirmed the diagnosis of primary chronic lymphoedema. The operation that consists of omentopexy (with vascularized omental flap) was the treatment of choice for this patient with favorable result. More than a year after the operation, the decreased difference in the circumference of lower limb for more than a 50% is maintained without any occurrence of new episodes of complications of lymphoedema.

PubMed - indexed for MEDLINE

Lymphedema of the limbs in rheumatoid arthritis

Clin Rheumatol. 1994 Sep Minari C, Cecconami L, Fioravanti A, Montemerani M, Scola C, Marcolongo R. Institute of Rheumatology, University of Siena, Italy.

The lymphedema of the extremities is a rare complication of rheumatoid arthritis (RA); it does not appear to be correlated with positivity for rheumatoid factor nor with the clinical activity of the disease. The authors describe 6 cases of lymphedema in patients affected by RA; in 3 of them the lymphoedema was localized in the upper and in the remaining cases in the lower limbs. Four patients, (one of whom has been subjected to a lymphoangiography which demonstrates an obstruction of the deep lymphatics), presented an increase of the plasma fibrinogen degradation products (FDP). This could confirm the hypothesis according to which the lymphoedema could be attributable to an obstruction of the lymphatics caused by fibrin and other degradation products of the coagulation system. In one case the authors underscore the therapeutic effectiveness of lymphodrainage associated with administration of diuretics.

PubMed

Lymphatic disorders in rheumatoid arthritis.

Semin Arthritis Rheum. 1993 Jun;

Joos E, Bourgeois P, Famaey JP. Department of Rheumatology and Physical Medicine, Saint-Pierre Hospital, Universities of Brussels, Belgium. Lymphedema is a rare complication of rheumatoid arthritis (RA). Diagnosis is clinical: long-standing, painful swelling of a whole limb in association with RA. Cases described in the literature are predominantly of the upper limbs, sometimes bilateral. Diagnosis can be confirmed by biopsy of lymph nodes, lymphography, or preferably lymphoscintigraphy. The etiology of the edema is unknown. Mechanical obstruction and lymphangitis have been suggested. Pharmacological and surgical treatment of the edema have been disappointing, and treatment of the underlying RA does not improve the lymphedema. Physical treatment of the affected limb, such as massage, manual drainage techniques, light compression bandaging, and exercise, has been moderately effective. PMID: 8342046 [PubMed - indexed for MEDLINE]

PubMed

Lymphedema of the leg associated with rheumatoid arthritis

Lymphology. 1991 Jun

Lacroix HR, Gruwez JA, Casteels-Van Daele MC, Dequeker J. Department of General Surgery, University Hospitals of Leuven, Belgium.

A 14-year-old boy with a two year history of seronegative rheumatoid arthritis developed left leg lymphedema and subsequently a severe episode of lymphangitis. The diagnosis of “rheumatoid lymphedema” was confirmed by lymphscintigraphy and conventional lymphography. Treatment consisted of bedrest and antibiotic drugs. When the signs of inflammation had subsided, therapy with corticosteroids was started with improvement of both joint pain and leg swelling. Whereas lymphedema associated with rheumatoid arthritis has been described in the upper limb of adults, to our knowledge this is the first report of the coexistent condition in the lower leg of a child. PMID: 1921478 [PubMed - indexed for MEDLINE]

PubMed

Lymphedema of the Limbs as an extra-articular feature of rheumatoid arthritis

September 1990

J. E. Dacre, D.L. Scott, E.C. Huskisson

Abstract

Seven patients with lymphedema of the hands and arms, an unusual extra-articular feature of rheumatoid arthritis are described. In all cases the lymphedema persisted throughout followup – in one case for more then five years – and was resistant to treatment with slow acting driugs, steroid, or cytotoxic agents. There was no correlation with severity of disease. It is concluded that the lymphedema in these patients may be associated with reduced numbers of lymphatic vessels; increased capillary permeability or abnormal fibrinolysis may also be contributory factors. Conservative management of such patients is recommended.

Patients with rheumatoid arthritis (RA) characteristically present with painful swollen hands and feet due to synovitis of their small joints. Lymphedema of the limbs can be an added complication in a small number of cases. Lymphedema of the upper limbs was first reported in RA by Kalliomaki and Vastamaki in 1968. Dudley Hart subsequently mentioned three cases in a review of the extra-articular features of R.A. Since then there have been three further report, and altogether 16 patients have been described. We have seen seven patients with this complication and report their clinical course, together with a review of the published findings.

Case Reports

Case 1

Age in years when seen 57; Sex – male; Site of lymphedema – hands; Onset of lymphedema after R.A. (years) less then one year; Rheumatoid factor – negative; Antinuclear antibody – negative; ESR – High; Radiology – Erosions; Outcome – minor improvement.

A 57 year old motor mechanic presented with painful swollen hands and prolonged morning stiffness which he had had for six weeks. He had no neurological symptoms. Examination showed bilateral lymphedema of the hands that extended to his wrists and inflammatory arthritis of the metacarpophalangeal joints. He had previously had poly myalgia rheumatics, which had been treated with steroids. He had concomitant diabetes mellitus and ischaemic heart disease. Tests for rheumataoid factor were negative and his erythrocyte sedimentation rate (ESR) was 35mm/first hour. Radiographs of his hands whoed an erosive arthritis. Seronagative RA was diagnosed. He was treated with inomethacin and showed symptomatic improvement. The lymphedema persisted. No other antiirheumatice drugs were given.

Case 2

Age in years when seen 52; Sex – male; Site of lymphedema – hands; Onset of lymphedema after R.A.8 years; Rheumatoid factor – positive; Antinuclear antibody – negative; ESR – very High; Radiology – Erosions; Outcome – minor improvement.

A 52 year old photographer had a 10 years history of classic RA of polymyalgic onset.

He had coexistent benign paraproteinaemia. He presented with a two year history of increased pain in his wrists and hands associated with diffuse swelling and considerable morning stiffness. Examination showed bilateral lymphedema of hands and forearms in association with active synovitis and pronounced joint destruction. Tests for rheumatoid factor were positive; the ESR was 64 mm/first hour. Radiographs of his hands showed symmetrical erosive changes. Electrophoresis showed an IgM monocloncal gammopathy. There was no evidence of lymphoma or myeloma despite extensive investigation. Lymphangiography was undertaken with difficult and showed no definite abnormality. He had previously been treated with gold and penicillamine with no alleviation of his symptoms. Subsequently treatment with hydroxychoroquine, prednisolone, and cyclophosphamide was unsuccessful. At the time of writing he was receiving sulphassalazine. The lymphedem persists, though it has shown some improvement.

Case 3

Age in years when seen 44; Sex – male; Site of lymphedema – hands; Onset of lymphedema after R.A. (years – 1 year; Rheumatoid factor – positive; Antinuclear antibody – positive; ESR – High; Radiology – No Erosions; Outcome – No change

A 44 year old publican presented with 18months of swollen stiff hands. He had some pain when first seen. This resolved, leaving persistent bilateral lymphedema of both hands and wrists that extended to the left elbow. Tests for rheumatoid factor were initially negative but were subsequently became positive. His ESR was 45 mm/first hour

Radiographs showed soft tissue swelling and periarticular osteoporosis without erosions. RA was diagnosed. Non-steroidal anti-inflammatory drugs were of minimal value, but he has not needed additional treatment. His lymphedema persists.

Case 4

Age in years when seen 51; Sex – female; Site of lymphedema – hands; Onset of lymphedema after R.A. (years) less then two years; Rheumatoid factor – negative; Antinuclear antibody – positive; ESR – Low; Radiology – Erosions; Outcome – No change.

A 51 year old woman with an 11 year history of classic RA developed painful swollen hands. Examination showed bilateral lymphedema. She had previously been treated with levamisole, but had relapsed, and, at the time of writing, was currently controlled on auranofin. Her ESR was 10 mm/first hors and she was rheumatoid factor negative. Radiographs of her hands showed fusion of both wrists joints with erosions affecting the metacarpophalangeal joints. She also had atlantoaxial subluxation. The lymphedema subsequently persisted for more than five years without regression.

Case 5

Age in years when seen 45 Sex – female; Site of lymphedema – hands; Onset of lymphedema after R.A. (years) 2 years; Rheumatoid factor – positive; Antinuclear antibody – NK; ESR – High; Radiology – Erosions; Outcome – no change.

A 45 year old woman with a 10 year history of classic RA presented with an eight year history of a swollen right hand. Examination showed unilateral lymphedema of the right hand with bilateral synovitis of the metacarpophalangeal joints. At presentation she was treated with azathioprine and has continued receiving that treatment. Her ESR was 50 mm/first hour; tests for rheumatoid factor were positive. Radiographs of her hands showed moderately severe erosive changes. The lymphedema has been resistant to treatment.

Case 6

Age in years when seen 62; Sex – male; Site of lymphedema – hands; Onset of lymphedema after R.A. (years)5 years; Rheumatoid factor – negative; Antinuclear antibody – negative; ESR – High; Radiology – Erosions; Outcome – no change

A 62 year old greengrocer presented with three years of polyarthritis which was diagnosed as RA. Mostperipheral joints were affected. He had had a history of Raynaud’s phenomenon since the age of 16. At presentation he had pronounced lymphedema of the left hand and forearm and the right hand. Radiography showed that this was an erosive arthritis. He was seronative for rheumatoid factor and also nagative for antinuclear antibodies. The ESR varied from 2 to 20 mm/first hour. A lymphangiogram showed no abnormality. The arthritis went into remission with non-steroidal anti-inflammatory drugs alone but the lymphedema of his hands persisted.

Case 7

Age in years when seen 54; Sex – female; Site of lymphedema – feet; Onset of lymphedema after R.A. (years) less then one year; Rheumatoid factor – positive; Antinuclear antibody – negative; ESR – High; Radiology – Erosions; Outcome – no change.

A 54 year old housewife developed acute polyarthritis in 1983 with the typical symmetrical and widespread distribution of RA. She had associated Raynaud’s phenomenon. She had a severely swollen right foot. Over the next few months she developed bilateral lymphedema of the feet extending up to the mid-calf. This varied in severity over the ensuing years. There was no evidence of venous thrombosis. Investigations showed an ESR of 30 mm/first hour which subsequently rose to over 100mm/ hour, remaining high. She was seropostive for rheumatoid factor. Tests for antinuclear antibodies and extractable nuclear antibodies were consistently negative. Radiographs showed widespread rheumatoid erosion. She received non-steroidal anti-inflammatory drugs, tetracosactrin acetate, and several slow acting drugs, including penicillamine and chlorambucil. HE RA remained active and the lymphedema persisted. In 1986 she developed radiological atlantoaxial subluxation.

Discussion

Lymphedema of the upper limbs is a rare extra-articular feature of RA. It can also affect the lower limbs, as shown in our final case (case 7), and those reported by Dudley Hart and Grillet et al. A total of twenty three patients with lymphedema have been described in their works. In 19 cases, it affected the upper limbs and in four the legs. It is more common in men; there were seven men out of the 13 cases for which the sex was known. It is not related to seropositivity for rheumatoid factor. There is no definite correlation with disease activity; although some cases have qui active RA, others have relatively mild disease.

The first report by Kallionmaki and Vastamaki described two Finnish women in middle age with serpositive R.A. Their lymphedema showed no obvious response to diuretics, steroids, or other drugs. These workers used lymphoscintigraphy with radiolabelled colloidal gold; the colloidal gold is injected subcutaneously and enters the lymph ducts and passes on to the regional lymph nodes. In normal subjects active accumlation is seen in the axillary nodes of the affected side, which suggested a local lymphatic blockage.

In some patients other mechanisms may lead to swelling of the forearms. Macfarlane and Vander Linden have described swelling in one man due to leaking olecranon bursitis. McCarty et al have reported pitting edema in remiiting seronative symmetrical synovitis. These patient have different problems from the 23 patients with lymphedema, and the changes might have reflected other pathological mechanisms. There may, however, be some features in common; our first patient had diabetes mellitus and the second patient an IgM paraprotein, and both of these might have contributed to increased lymphatic permeability and part of the upper limb swelling. Jayson and Barkes have shown that there are changes in capillary permeability in RA with increased filtration of tissue fluid. In some cases this might have contributed towards the lymphedema.

Abnormal fibrinolytic mechanisms in RA might also play a part by leading lymphatic obstruction.

Most reports have included lymphgraphic studies. We only undertook this in two cases and the investigation was unsuccessful. The finding on lymphography are usually of dilated proximal lymph vessels, extravasation of contrast material and dermal reflux. We felt that the clinical picture was characteristic and that lymphangiograms were unpleasant, and not necessary for management. The lymphangiograms undertaken in the patients with RA and lymphedema reported previously suggest that the principal cause of the lymphedema is blockage of the deep lymph vessels. Grillet and Dequeker considered that the procdss might have been due to an inflammatory lymphangitis, which is similar to the vasculitis of RA. The evidence for this is weak, and an alternative possiblility is that there are reduced numbers of lymphatics in rheumatoid patients, which can readily become obstructed by fibrin and related products. In either case there is no definite improvement after aggressive treatment with steroids, slow acting antirheumatic drugs and cytotoxic agents. We recommend conservative manageent of such patients with limited investigation.

PubMedArchive

Limb Lymphedema in Rheumatoid Arthritis

Annals of the Rheumatic Diseases June 1991

A Bamji – Physician Response to a previous article.

Sir: There is an alternative, and simpler explanation for limb lymphedema in rheumatoid arthritis as reports by Dacre, Scott and Huskisson – obstruction. The report by Macfarlane and van der Linden hints at this; edema in their case was associated with a leaking olecranon bursa, but ‘after injection of corticosteroid into the bursa and elevation of the arm the forearm swelling resolved almost completely.’

I have seen four cases of severe limb edema in inflammatory arthritis.

Case 1

A 56 yearold housewife with a 15 year history of seropostive rheumatoid arthritis. This was atypical, with involvment of large and medium sized joints and complete sparing of the small joints of the hands, though there was erosive change at the wrists. Both elbows were affected, with moderate destructive change, fixed flexion deformity, and lateral instability, especially on the right. She had had both knees and hips replaced.

She developed slow onset pitting edema of the right forearm and hand, which caused severe limitation of function and was very painful. This failed to respond to elevation of the arm and persisted for over a year despite continuing steroids by mouth. She was reviewed by the orthopaedic department, who suggested that the edema might be due to obstruction of venous or lymphatic return at the elbow, and accordingly I injected the elbow with triamcinolone. Over the nesk week the edema resolved completely. Two years laer it has not recurred, though the elbow continues to produce some pain.

Case 2

A 72 year old man was referred with ahistory of sudden painful swelling of the right wrist. A previous diagnosis of seronative rheumatoid arthritis and coincident psoriasis had been made elsewhere two years previously, and he had been treated since with 5 mg prednisolone on alternative das and gold injections he was also taking diuretics for mild cardiac failure and hypertension. He had been free from symptoms in the joints for many months until the sudden flare in the wrist.

When I first saw him, the wrist was quiet (the steroids had been increased for a week to 40 mg daily), but on review one month later the whole hand was swollen, painful, tender, and edemous, looking almost gouty. He was unable to flex the fingers because of the edema. After one month’s treatment with diclofenac and splinting the wrist and hand were unchanged. I injected the wrist with triamcinolone. Within a few days the edema has disappeared. Although he has some finger stiffness, the edema remains absent 14 months later.

Case 3

A 67 year old woman with a past history of myocardial infarction and severe peripheral vascular disease requiring bypass surgery was referred with a short history of pain and swelling in the small joints, especially the hands, and bilateral carpal tunnel syndrome. Her sister had severe rheumatoid arthritis.

Examination confirmed small joint polyarthritis. She was treated with wrist splints and diclofenac with improvement of the carpal tunnel symptoms, but overall she was worse and treatment was started with prednisolone 7.5 mg daily. She had side effects, however, and stopped these, continuing to receive diclofenac only.

Four months after presentation she atteneded for f=routine review with a painful swollen hand. The wrist as stiff and tender, but the striking feature was severe pitting edema of the hand. I injected the wrist with triamcinolone. The edema disappeared within four days and three months later has not recurred.

Case 4

A 60 year old man was referred with a short history of unilateral ankle pain and swelling. He had previous foot and knee symptoms suggestive of osteoarthritis. On examination the skin over the ankle felt very tight. Thre was no obvious edema and he had no pain on movement. Both feet were flat.

The ankle was injected , and improved. He developed some foot numbness suggestive of tarsal tunnel syndrome and arch insoles were prescribed, but he then defaulted from the clinic.

He was re-referred six months later with shoulder pain, apparently due to supraspinatus tendonitis, but on review two months later had developed generalized inflammatory type symptoms affecting hands shoulders, and knees, which responded only partly to anti-inflammatory drugs. Then quite suddenly he developed swelling of his left knee and leg. On examination he had a tense knee effusion with a popliteal cyst and severe pitting edema of the leg and foot. The leg above the knee was normal.

The knee was injected with triamcinolone, though no fluid was aspirated. Initially, both the knee and edema subsided slightly but then worsened again and he attended the accident department and was admitted for treatment by the orthopaedic surgeons, who aspirated 80 ml turbid fluid without injecting steroid, pending my outpatient appointment 10 days later. The edema again abated, but the knee effusion reaccumulated and the leg swelling reappeared.

The response of the edema in each case to injection of the joint just proximal is surely not coincidence. Just as peripheral nerves can be compressed when there is soft tissue swelling, thickening, or inflammation, so can veins and the lymphatic system. It is interesting in this contect that non of the above patients had nerve root compression symptoms.

Apart from Macfarlane’s case, none of the patient in Dacre’s series or in the quoted references had joint inj4ections. I suggest it is tried more often Andrew Bamji Frognal Centre for Medical Studies Queen Mar’s Hospital Sidcup Kent DA14 6LT

PudMed

Lymphatic Obstruction in rheumatoid arthritis: a cause for upper limb edema

Annals of Rheumatology June 1980

R.T.D. de Silva, D.M. Grennan, and D.G.Palmer Departments of Radiolgoy and Medicine, University of Otago Medical Schools, Dunedin, New Zealand.

Summary: Periepheral lymphatic obstruction has been demonstrated by lymphangiography as a cause of upper limb edema in 2 patients with seronegative rheumatoid disease.

A small portion of patients with rheumatoid arthritis develop peripheral edema which appears to be more widespread than can be attributed to inflammatory synovitis involving the regional joints and which cannot be related to general factors such as anaaemia, hypoalbuminaemia, or generalized fluid retention. The results of previous studies have suggested that such edema may be the result of venous obstruction (Swinburne, 1964), of a generalized increased in capillary permeability (Jayson and Barks, 1971), or of lymphatic obstruction (Kalliomaki and Vastamaki, 1968) Some of these previous studies have examined patients with edema of the lower limbs only (Sinburne, 1964; Jayson and Barks, 1971; Jayson et al., 1971), a situation in which such factors as immobility and generalized fluid retention are difficult to exclude.

In contrast, when edema of the hands and forearms accompanies rheumatoid arthritis, such causes of fluid retention can ordinarily be discounted if dependent edema does not involve the lower limbs. In this paper 5 rheumatoid patients with edema of the upper limbs and 2 with edema of the lower limbs were investigated by lymphangiography. In 2 of the patients with hand and forearm edema unequivocal lymphangiographic evidence of lymphatic obstruction was found.

Patients and methods

Patients with Lymphangiographic Evidence of Lymphatic Obstruction

Case 1 was a 56 year old woman who presented with an 8-month history of shoulder pain and a 6-week history of pain in the knees. Bilateral knee effusions were present. The sheep cell agglutination test was consistently negative, but articular erosions appeared. Swelling over the dorsum of the right wrist was noted 9 months later. Six years after the onset of symptoms the right forearm and hand became diffusely swollen with pitting of the edema and some 4 months later the left forearm and hand were similarly involved. Finger movements remained full despite erosive changes having developed in the wrists and various small joints of the hands. The swelling was said to fluctuate but on one occasion was observed to extend to the elbows. On another occasion, after aspiration of a knee joint and injection of a corticosteroid preparation the upper arm edema was observed to resolve within 48 hours of the procedure only to reappear gradually over the subsequent weeks. The patient was receiving sodium aurothiomalate and soluble aspirin at the time the forearm edema appeared.

Case 2 was a 57 year old woman who developed seronative erosive rheumatoid arthritis 12 years before presenting with diffuse pitting edema of the right hand and forearm. Her treatment at this time consisted of sodium aurothiomalate and ibuprofen. The course of her arthritis had tended tobe episodic, and multiple joints including the shoulders, elbows, wrists, knees, and ankles had been involved. Involvement of the flexor sheaths of the fingers and the extensor sheaths at the wrists had been noted.

Swelling of the right forearm persisted for 6 months before resolving completely, but this was shortly followed by similar swelling of the left hand and forearm. Nine months later both forearms were noted to be simultaneouslt involved, and after yet a further 3 months all swelling had completely disappeared. The episodes of forearm edema were not associated with either signs of increased disease activity in the wrists, finger joints (although erosions involved these joint), or elbows, or with any generalized flare. Edema did not involve the legs at any time, and no changes in anti-inflammatory drug therapy had been lade which could have been related to the episodes of forearm swelling.

Patients with Upper Limb Edema in Whom Lymphatic Channels Could Not Be Demonstrated

The next three patients all had erosive disease which involved various small joints of the fingers and the wrists.

Case 3 had swelling of the right hand and forearm for about 18 months before the left was similarly affected. This patient’s disease was atypical in theat massive synovial hypertrophy of the right subacromial burse of the type described by Kent et al. (1978) was an early sign, and synovectomy of this bursa preceded swelling of the right hand by 9 months. The left subacromial bursa became similarly involved. Swelling of the left hand followed involvement of the ipsilateral shoulder by 18 months, but preceded the synovectomy eventually performed on this side.

Case 4 had had edema of the right hand and wrist for 5 months before lymphangiography was undertaken. This patient also has von Willebrand’s disease.

Case 5 has chronic progressive disease.

These 3 patients were all receiving a slicylate. In addition case 3 was receiving indomethacin and case 3 was receiving indomethacin and case 5 ibuprofen. In no case had hypoproteinaemia been detected.

Patients with Lower Limb Edema

Patients 6 and 7 were both thought to have developed more extensive edema of the lower limb than expected from the disease activity of the lower limb joints; nevertheless case 6 had hips, knees, and ankles involved, and case 7 had effusions in both knees. No other cause for the edema was detected. Both patients were receiving indomethacin and in addition case 6 ibuprofen and case 7 a salicyclate.

Lymphangfiography

The technique adopted for lymphagiography was that described by Kinmonth (1952). Paten blue dye was injected into all the interdigital webs of the affected hand or foot. It was not possible to see subcutaneous lymphatics through the skin in any patient because of the presence of edema. An exploratory incision was made on the dorsum of the hand or foot just distal to the wrist or ankle joint.

Where visible, a subcutaneous lymphatic channel was cannulated and 2 ml of iodised oil ultrafluid (Lipiodol) slowly injected over a period of 40 minutes. Radiographs were obtained immediately after the procedure in case 1, and in case 2 the procedure was modified and radiographs were obtained at 5 minute intervals during the injection period. In both cases further films were obtained 24 hours later. A similar procedure was followed in the 2 patients in who, the leg lymphatics were studied.

Results

Radiological evidence of edema, that is, blurring of the fascial-fat interface, increased depth of the subcutaneous tissues, and prominence of the neurovascular pedicales, extended more proximally then was judge to be the case clinically.

Case 1

Complete obstruction of the subcutaneous lymphatic channels associated with dermal backflow into the hand and extravasation into the perivenous tissues was demonstrated after perfusion with Lipiodol. The dermal backflow obscured the cannulated channel and indicated the need for the serial films taken in the second case. Subcutaneous lymphatic channels of the upper arm were not outline during the initial examination but were apparent after a period of 24 hours.

Case 2

The cannulated subcutanoues lymphatic channel was outlined as far as the proximal row of carpal bones. The contrast medium instead of transversing the subcutaneous lymphatic channel refluxed back into the dermal lymphatics as a result of the obstruction. Lymphatic flower beyond the wrist joint was maintained only by the dermal lymphatics. The 24-hour films demonstrate perivenous extravasation and lymphstasis and lymph nodes contained small filling defects situated in the forearm.

Cases 3, 4, and 5

These were the 3 further patients with upper limb edema in whom no lymphatic channels were found on cut-down following the injection of patient blue dye, and the lymphaiographic procedure was abandoned.

Cases 6 and 7

In both of these 2 patients with lower leg edema normal lymphatic channels were demonstrated. The regional lymph nodes (inguinal, pelvic, and paraaortic) were rounded but showed the accentuated punctate pattern of nodular hyperplasia.

Discussion

This study has provided convincing lymphangiographic evidence that lymphatic channel obstruction is responsible for diffuse edema of the hand and forearm in some patients with rheumatoid disease. In both patients with upper limb edema in who, a subcutaneous lymphatic channel was succedssfully cannulated the classical changes secondary to mechanical obstruction – dermal backflow, lymphystasis, and perivenous extravasation – were demonstrated. Physical properties of Lipiodol ultrafluid are such that the lymphatic channels are not outlined unless there has been successful cannulation of a subcutaneous lymphatic. If Lipiodol ulstrafluid is injected into the tissues after an unsuccessful cannulation, the contrast medium remains at the site of injection and does not enter the lymphatics. The phenomenon of dermal backflow indicates that there is obstruction to the onward flow of lymph (Craig 1969). In a normal subject injection of this contrast medium into a subcutaneous lymphatic results in this channel and its branches being outlined during the onward flow of the medium being retained for more than 24 hours with normal lymphatics, and retention beyond this period is in keeping with proximal obstruction. Contrast medium that extravasates from obstructed lymphatics accumulates in the loose perivenous areolar tissues.

In the second patient the contrast medium instead of directly traversing the cannulated subcutaneous lymphatic refluexed back into the dermal lymphatics at the level of the wrist and in this manner bypassed the obstruction. It should be noted that the dermal lymphatics themselves are so minute that they cannot be cannulated, whereas the subcutaneous lymphatics in the hand measure approximately a third of a millimeter in diameter in the undistended state.

In the presences of gross edema subcutaneous injection of patient blue dye may not outline the lymphatics, as the dye diffuses into the edemous tissues, and attempts to locate lymphatics may thus be unsuccessful. In the 3 further patients with rheumatoid disease with similar edema of the forearms it was not possible to demonstrate lymphatics with the patient blue dye technique after cutdown. It is impossible to state whether this observation reflected extensive obliteration of lymphatics in these patients or was the effect of the edema Exploratory incision proximal to the edge of the blue dye as was undertaken in these patients is always worthwhile before a decision is made to abandon this investigation.

In neither patient did the lymph nodes of the upper limb appear to be significantly enlarged wither on palpation or on the lymphangiogram, nor was there any evidence to suggest that any obstruction to lymph flow was occurring at the nodes. The filling defects noted were compatible with germinal center hypertrophy and have been noted previously (Robertson et al, 1968).

All 5 patients with upper limb edema had erosive rheumatoid disease which involved the wrists, and both patients In whom it was possible to demonstrate lymphatic obstruction were seronegative. In 3 of these 5 patients the edema became bilateral, and in 1 of the remaining 2 the swelling was of relatively recent onset. Spontaneous regression and temporary regression following distant corticosteroid injection was observed. Pain and signs of inflammation other than that directly associated with adjacent joint disease were not features.

Them demonstration of normal lymphatic channels in the 2 patient with lower limb edema emphasizes the difficulty in differentiating the various possible causes of dependent edema in rheumatoid disease and does not exclude the possibility that similar lymphatic obstruction to that seen in the upper limbs may on occasion involve the legs.

It is possible that an inflammatory arthritis developing in a patient with some –pre-existing anatomical or functional deficiency of the lymphatic system might result in peripheral edema. It is more likely that lymphatic obstruction might result from the direct extension of the inflammatory process from involved joints to the surrounding tissues or be a consequence of immune complexes reaching these channels and initiating a chronic lymphangitis. There was no suggestion, however, that there had been any acute additional event likely to lead to extension of the inflammatory process such as secondary joint infection or snyovial rupture.

Our findings are in keeping with the lymphoscitigraphic study of Kallionmaki and Vastamaki (1968), in which evidence of lymphatic obstruction was found in 2 rheumatoid patients with unilateral upper limb edema. Most previous studies have, however, investigated rheumatoid patients with lower limb edema (Swinburne, 1964; Jayson and Barks, 1971) and have concluded that lymphatic obstruction was not the cause of edema. In a subsequent study Jayson et all (1971) made us of the local clearance rate of intrademally injected radiolabelled albumin as an index of lymphatic flow rates, and, although they found that this was slowing was actually markerd in patient with edema than in those without and concluded that lymphatic obstruction was not responsible. This study can be critised on the grouns that locally injected albumin has been shown to be cleared by both venous and lymphatic routes (Sage et al., 1964), suggesting that this method does not give a specific indication of lymphatic flow rate.

The present study has demonstrated that in some patients with rheumatoid edema of the upper limbs, lymphatic obstruction does occur. The clearance rate of the inert gas radioactive xenon (133Xe) from a region following local injection has been used as an index of the adequacy of its nutrient blood flow and venous drainage (Sejrsen, 1967; Grennan et at., 1975). Normal local clearance rates of xenon were obtqined from one of our patients (not performed in the other) in who, lymphagiography demonstrated lymphatic blockage, suggesting that the venous flow was not significantly impaired in this patient.

One might also speculate whether lymphatic obstruction may contribute to presistentjoin effusion in rheumatoid disease. Kuhns (1933) described the apparent obliteration of snynovial lymphatics in patients with joint inflammation, an observation which suggests that ab obliterative (personal communication), however, regards contrast filled lymphatics as a rather specific feature which accompanies the rheumatoid arthrogram. These apparently opposing observations are difficult to reconcile unless the latter phenomenon represent dilation of residual channels.

PubMed

Efficacy of etanercept and complete decongestive physical therapy in bilateral lower-limb lymphoedema associated with rheumatoid arthritis: A case report.

Adv Ther. 2008 Jan-Feb

Eyigor S, Karapolat H, Kirazli Y. Department of Physical Therapy and Rehabilitation, University of Ege, Faculty of Medicine, 35100, Bornova, Izmir, Turkey, eyigor@hotmail.com.

Keywords etanercept - lymphoedema - rheumatoid arthritis - treatment - lymphedema

A 54-y-old patient with rheumatoid arthritis (RA) and bilateral lower-limb lymphoedema is presented. Complete decongestive physical therapy (CDP) is the cornerstone of the management programme in all patients suffering from lymphoedema associated with RA, but it is not clear which therapy is the most effective in decreasing the oedema. We report on a patient with bilateral lower-limb lymphoedema associated with RA who, after receiving etanercept and CDP, showed moderate improvement. There is little information on the benefit of etanercept therapy for the extra-articular manifestations of RA. Further research is necessary to confirm the beneficial effect of etanercept and CDP.

Springer Link

Juvenile rheumatoid arthritis and lymphoedema: lymphangiographic aspects

Pediatr Radiol. 1999 May

Schmit P, Prieur AM, Brunelle F. Service de Radiopédiatrie, Groupe Hospitalier Necker-Enfants-Malades, Paris, France.

We report a 5 1/2-year-old boy with juvenile rheumatoid arthritis (JRA) and lower-limb lymphoedema. US, MRI and lymphangiography were performed. Based on the lymphangiographic study, we propose a pathogenesis based on obstruction of normal superficial lymphatic vessels in the affected limb. This is discussed with other pathogenetic factors proposed in the 16 previously reported cases of lymphoedema complicating JRA.

Springer Link

Idiopathic limb edema in children with chronic arthritis: a multicenter report of 12 cases

Rheumatol. 1997 Feb

Bardare M, Falcini F, Hertzberger-ten Cate R, Savolainen A, Cimaz R. First Pediatric Department, University of Milano, Italy.

Lymphedema, a well known extraarticular manifestation of rheumatoid arthritis, has been rarely described in children with idiopathic chronic arthritis. We describe 12 cases of lymphedema and idiopathic arthritis of childhood seen at 4 different pediatric rheumatology centers. Eight patients were girls, 4 boys; the age at appearance of lymphedema ranged from 2.3 to 17 years. In all patients except one, lymphedema was localized to the lower limbs. The outcome of lymphedema was variable, but not always related to the arthritis course, and was mostly independent of any specific therapy. Lymphography was performed in only one patient, and revealed lack of lymphatic drainage in the affected leg. We conclude that the association of lymphedema and idiopathic arthritis of childhood is not rare; this association is unlikely to be coincidental, even though the pathogenetic mechanisms are currently not well understood.

PMID: 9035001 PubMed - indexed for MEDLINE

Upper limb lymphedema associated with polyarthritis of rheumatoid type

Kiely PD, Joseph AE, Mortimer PS, Bourke BE. Department of Rheumatology, St. George's Hospital, London, England.

J Rheumatol. 1994 Jun

OBJECTIVE. To determine the cause of upper limb edema in 8 patients with peripheral polyarthritis of rheumatoid-type.

METHODS. Objective assessment of lymph function using quantitative lymphoscintigraphy.

RESULTS. Seven cases with either rheumatoid or psoriatic arthritis were found to have impaired lymph drainage associated with edema. All cases shared a distal rheumatoid pattern of arthritis but showed no relation between severity of lymphatic impairment and either duration or severity of arthritis.

CONCLUSION. Polyarthritis of rheumatoid-type may be associated with lymphedema due to impaired lymphatic function.

PubMed

Lymphoscintigraphic study in a case of rheumatoid arthritis-related lymphoedema

Clin Exp Rheumatol. 1993 Jul-Aug

Hidalgo Calleja C, Cuesta Andrés M, Llorente Melero MJ, Espinosa Castelló A, Balsa Criado A, Gijón Baños J. Rheumatology Unit, Hospital La Paz, Madrid, Spain.

Lymphoedema of the upper limbs is a rare extraarticular manifestation of rheumatoid arthritis (RA). Herein we report a patient with RA who presented two episodes of lymphoedema in the hands and forearms coinciding with flares of polyarthritis. Lymphoscintigraphy showed lymphatic-ectasia. The oedema improved with slow-acting drug treatment.

PubMed

Rheumatoid lymphoedema

Clin Rheumatol. 1982 Jun

Kyle VM, De Silva M, Hurst G. Bilateral upper limb oedema due to lymphatic obstruction, is an uncommon complication of rheumatoid arthritis (R. A.). We report a case in which a 40 year old male with seropositive rheumatoid arthritis developed gross pitting oedema of the left arm. Lymphangiography showed lymphatic obstruction in both arms; within two months the right arm also became oedematous.

PMID: 6926809 PubMed - indexed for MEDLINE

The demonstration of lymphatic channels on wrist arthrography in rheumatoid disease with particular reference to associated lymphedema

Wu G., Whitehouse GH, Littler TR

Delineation of lymphatic vessels is a frequent finding in arthrograms of rheumatoid joints. Arthrography of the rheumatoid wrist when associated with oedema of the upper limb reveals a characteristic pattern consistent with lymphatic obstruction. In our opinion, these findings may be regarded as further evidence in favour of lymphatic obstruction as the cause of peripheral oedema in rheumatoid arthritis. The syndrome appears to be a separate entity from idiopathic oedema of women.

Oxford Journal

Prostaglandins, rheumatoid arthritis, fibrin and lymphoedema

Agents Actions Suppl. 1979

Jasani MK, Bach CS. Rheumatoid joint swelling is in part due to lymphoedema accompanying extravascular (E-V) deposition of fibrin. Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin (ASA), phenylbutazone (PBZ) and indomethacin (INDO) which share the ability to inhibit prostaglandin synthetase fail to prevent fibrinous lymphoedema occurring in rabbit skin homografts in association with the presence of sensitised lymphocytes. The data highlight the need to define whether or not prostaglandins promote lymphocytic fibrinous lymphoedema.

PubMed

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