Remitting seronegative symmetrical synovitis with pitting edema (abbreviated RS3PE or sometimes RS₃PE) is a rare syndrome

Syndrome

In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...

 identified by symmetric polyarthritis

Polyarthritis

Polyarthritis is any type of arthritis which involves 5 or more joints simultaneously. It is usually associated with autoimmune conditions.Polyarthritis may be experienced at any age and is not gender specific.-Causes:...

, synovitis

Synovitis

Synovitis is the medical term for inflammation of the synovial membrane. This membrane lines joints which possess cavities, known as synovial joints. The condition is usually painful, particularly when the joint is moved. The joint usually swells due to synovial fluid collection.Synovitis may...

, acute pitting edema

Edema

Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...

 of the back of the hands and/or feet, and a negative serum

Serum

Serum may refer to:*Blood serum, a component of blood which is collected after coagulation.**Antiserum, blood serum with specific antibodies for passive immunity*Serous fluid, any clear bodily fluid*any drug derived from an animal's blood or serous fluid...

 rheumatoid factor

Rheumatoid factor

Rheumatoid factor is an autoantibody most relevant in rheumatoid arthritis. It is defined as an antibody against the Fc portion of IgG. RF and IgG join to form immune complexes that contribute to the disease process...

.
If no underlying disorder can be identified (idiopathic

Idiopathic

Idiopathic is an adjective used primarily in medicine meaning arising spontaneously or from an obscure or unknown cause. From Greek ἴδιος, idios + πάθος, pathos , it means approximately "a disease of its own kind". It is technically a term from nosology, the classification of disease...

 RS3PE), this entity has an excellent prognosis and responds well to treatment.

RS3PE typically involves the joints of the extremities, specifically the metacarpophalangeal

Metacarpophalangeal joint

The metacarpophalangeal joints are of the condyloid kind, formed by the reception of the rounded heads of the metacarpal bones into shallow cavities on the proximal ends of the first phalanges, with the exception of that of the thumb, which presents more of the characters of a ginglymoid joint...

 and proximal interphalangeal joints, wrist

Wrist

In human anatomy, the wrist is variously defined as 1) the carpus or carpal bones, the complex of eight bones forming the proximal skeletal segment of the hand;...

s, shoulder

Shoulder

The human shoulder is made up of three bones: the clavicle , the scapula , and the humerus as well as associated muscles, ligaments and tendons. The articulations between the bones of the shoulder make up the shoulder joints. The major joint of the shoulder is the glenohumeral joint, which...

s, elbow

Elbow

The human elbow is the region surrounding the elbow-joint—the ginglymus or hinge joint in the middle of the arm. Three bones form the elbow joint: the humerus of the upper arm, and the paired radius and ulna of the forearm....

s, knee

Knee

The knee joint joins the thigh with the leg and consists of two articulations: one between the fibula and tibia, and one between the femur and patella. It is the largest joint in the human body and is very complicated. The knee is a mobile trocho-ginglymus , which permits flexion and extension as...

s and ankle

Ankle

The ankle joint is formed where the foot and the leg meet. The ankle, or talocrural joint, is a synovial hinge joint that connects the distal ends of the tibia and fibula in the lower limb with the proximal end of the talus bone in the foot...

s.
It is more common in older adults

Old age

Old age consists of ages nearing or surpassing the average life span of human beings, and thus the end of the human life cycle...

, with the mean age between 70 and 80 years in most studies.
It occurs more often in men than in women with a 2:1 ratio.
It is unknown how common this condition is.

Causes

RS3PE is a constellation of symptoms that can be caused by many other conditions. Since there is no definitive diagnostic test, other conditions have to be ruled out

Differential diagnosis

A differential diagnosis is a systematic diagnostic method used to identify the presence of an entity where multiple alternatives are possible , and may also refer to any of the included candidate alternatives A differential diagnosis (sometimes abbreviated DDx, ddx, DD, D/Dx, or ΔΔ) is a...

 before this rare condition can be diagnosed.

The main differential diagnosis is polymyalgia rheumatica

Polymyalgia rheumatica

Polymyalgia rheumatica , abbreviated as PMR, is a syndrome with pain or stiffness, usually in the neck, shoulders, and hips. The pain can be very sudden, or can occur gradually over a period of time...

 (PMR), although pain, stiffness and weakness at the level of the shoulders and pelvic girdle with associated systemic symptoms (fever

Fever

Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...

, malaise

Malaise

Malaise is a feeling of general discomfort or uneasiness, of being "out of sorts", often the first indication of an infection or other disease. Malaise is often defined in medicinal research as a "general feeling of being unwell"...

, fatigue, weight loss

Weight loss

Weight loss, in the context of medicine, health or physical fitness, is a reduction of the total body mass, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue...

) is more typical of PMR. Prospective studies have found a subgroup of PMR patients with hand edema, as well as other similarities. Thus, RS3PE has been proposed as a condition related to PMR or even that they are both part of the same disorder. However, PMR typically requires protracted courses of steroids, whereas corticosteroids can be tapered more quickly with persisting remission in RS3PE.

Other rheumatological disorders that can cause the features typical for RS3PE include late onset (seronegative) rheumatoid arthritis

Rheumatoid arthritis

Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...

, acute sarcoidosis

Sarcoidosis

Sarcoidosis , also called sarcoid, Besnier-Boeck disease or Besnier-Boeck-Schaumann disease, is a disease in which abnormal collections of chronic inflammatory cells form as nodules in multiple organs. The cause of sarcoidosis is unknown...

, ankylosing spondylitis

Ankylosing spondylitis

Ankylosing spondylitis , previously known as Bekhterev's disease, Bekhterev syndrome, and Marie-Strümpell disease is a chronic inflammatory disease of the axial skeleton with variable involvement of peripheral joints and nonarticular structures...

 and other spondyloarthropathies such as psoriatic arthropathy, mixed connective tissue disease

Mixed connective tissue disease

In medicine, mixed connective tissue disease , commonly abbreviated as MCTD, is an autoimmune disease, in which the body's defense system attacks itself. It was characterized in 1972....

, chondrocalcinosis and arthropathy due to amyloidosis

Amyloidosis

In medicine, amyloidosis refers to a variety of conditions whereby the body produces "bad proteins", denoted as amyloid proteins, which are abnormally deposited in organs and/or tissues and cause harm. A protein is described as being amyloid if, due to an alteration in its secondary structure, it...

.

RS3PE has been documented in patients with cancer

Cancer

Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

s (Non-Hodgkin's lymphoma, gastric cancer, pancreatic cancer

Pancreatic cancer

Pancreatic cancer refers to a malignant neoplasm of the pancreas. The most common type of pancreatic cancer, accounting for 95% of these tumors is adenocarcinoma, which arises within the exocrine component of the pancreas. A minority arises from the islet cells and is classified as a...

, lung cancer

Lung cancer

Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...

, breast cancer

Breast cancer

Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...

, colon cancer, prostate cancer

Prostate cancer

Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...

 and bladder cancer, among others), in whom it might represent a paraneoplastic manifestation.
Other underlying disorders include vasculitides

Vasculitis

Vasculitis refers to a heterogeneous group of disorders that are characterized by inflammatory destruction of blood vessels. Both arteries and veins are affected. Lymphangitis is sometimes considered a type of vasculitis...

 such as polyarteritis nodosa

Polyarteritis nodosa

Polyarteritis nodosa is a vasculitis of medium & small-sized arteries, which become swollen and damaged from attack by rogue immune cells. Polyarteritis nodosa is also called Kussmaul disease or Kussmaul-Maier disease...

.

Other causes of edema include heart failure, hypoalbuminemia

Hypoalbuminemia

Hypoalbuminemia is a medical condition where levels of albumin in blood serum are abnormally low. It is a specific form of hypoproteinemia.Albumin is a major protein in the human body, making up about 60% of total human plasma protein by mass...

, nephrotic syndrome

Nephrotic syndrome

Nephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein from the blood into the urine....

 and venous stasis

Venous stasis

Venous stasis, or venostasis, is a condition of slow blood flow in the veins, usually of the legs. A patient with venous stasis might be more vulnerable to the formation of blood clot, especially in the deep veins of the legs, called deep vein thrombosis .Causes include long periods of immobility...

. The key distinguishing feature is that these conditions don't tend to manifest with pitting edema at the back of the hands.

Diagnosis

Ultrasonography and magnetic resonance imaging of the hands and/or feet have been proposed as useful diagnostic investigations in RS3PE.

Some studies linked RS3PE to HLA-B27

HLA-B27

Human Leukocyte Antigen B27 is a class I surface antigen encoded by the B locus in the major histocompatibility complex on chromosome 6 and presents antigenic peptides to T cells...

 whereas others have not.

Treatment

RS3PE responds excellently to low dose corticosteroids, with sustained and often complete remission. Non-steroidal anti-inflammatory drugs (NSAIDs) have also been used. Hydroxychloroquine

Hydroxychloroquine

Hydroxychloroquine is an antimalarial drug, sold under the trade names Plaquenil,Axemal, Dolquine, and Quensyl, also used to reduce inflammation in the treatment of rheumatoid arthritis and lupus...

 has proven effective in some cases.

Disease mechanism

The disease mechanism (pathophysiology) of RS3PE remains unknown. One study suggested a possible role for vascular endothelial growth factor

Vascular endothelial growth factor

Vascular endothelial growth factor is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate....

. A study using magnetic resonance imaging

Magnetic resonance imaging

Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...

 found that tenosynovitis

Tenosynovitis

Tenosynovitis is the inflammation of the fluid-filled sheath that surrounds a tendon. Symptoms of tenosynovitis include pain, swelling and difficulty moving the particular joint where the inflammation occurs. When the condition causes the finger to "stick" in a flexed position, this is called...

 of the extensors of the hands and feet is the major contributor to edema.

History

In a 1985 paper published in the Journal of the American Medical Association

Journal of the American Medical Association

The Journal of the American Medical Association is a weekly, peer-reviewed, medical journal, published by the American Medical Association. Beginning in July 2011, the editor in chief will be Howard C. Bauchner, vice chairman of pediatrics at Boston University’s School of Medicine, replacing ...

, McCarty and colleagues first described a case series of patients with this disorder, for which they coined the abbreviation RS3PE.