Schnitzler syndrome
Encyclopedia
Schnitzler syndrome is a rare disease
characterised by chronic
hives (urticaria) and periodic fever
, bone pain
and joint pain
(sometimes with joint inflammation
), weight loss
, malaise
, fatigue, swollen lymph glands and enlarged spleen and liver
.
The urticarial rash is non-itching in more than half of cases, which is unusual for hives. It is most prominent on the trunk, arms and legs, sparing the palms, soles, head and neck. Associated angioedema
has been reported in a few patients. A review of 94 cases found a mean age at onset of 51 years, and only four patients developed symptoms before the age of 35. The cause and disease mechanism of Schnitzler syndrome remain largely unknown.
Schnitzler syndrome is considered an autoimmune disorder. Chronic hives and a monoclonal gammopathy
have been proposed as the major criteria, while the others represent minor criteria.
s show a high concentration of specific gamma-globulins (monoclonal gammopathy) of the IgM
type. It almost always has light chains
of the κ-type. A variant in which IgG is raised has been described, which appears to be ten times as rare. The immunoglobulins may show up in the urine as Bence Jones protein
s. Signs of inflammation are often present: these include an increased white blood cell
count (leukocytosis
) and a raised erythrocyte sedimentation rate
and C-reactive protein
. There can be anemia of chronic disease
. Bone abnormalities can be seen on radiological imaging
(often increased density or osteosclerosis
) or biopsy
.
Because it is such a rare condition (less than 100 cases reported in the literature worldwide before 2008), it is important to rule out other conditions
which can cause periodic fevers, paraproteins or chronic hives. These include (and are not limited to) auto-immune or -inflammatory disorders such as adult-onset Still's disease
, angioedema
, hematological disorders such as lymphoma
or monoclonal gammopathy of undetermined significance
, other causes of hives, cryoglobulinemia
, mastocytosis
, chronic neonatal onset multisystem inflammatory disease
or Muckle-Wells syndrome
.
It is however possible to have more than one rare condition as seen by a patient with Schnitzler's syndrome and cold induced urticaria.
. AA amyloidosis
has also been reported in people with Schnitzler syndrome.
drugs such as corticosteroids, cyclooxygenase inhibitors, interferon alpha, interleukin 1 receptor antagonist
s (Anakinra
), perfloxacin, colchicine
, cyclosporine or thalidomide
. The hives may respond to treatment with PUVA
, and the bone pain may respond to bisphosphonates.
in 1972.
There is a Facebook page entitled "Schnitzler's syndrome", which has been set up as a forum for support, discussion and sharing experiences and information. It is open access and anybody with an interest in the condition is very welcome to participate.
Rare disease
A rare disease, also referred to as an orphan disease, is any disease that affects a small percentage of the population.Most rare diseases are genetic, and thus are present throughout the person's entire life, even if symptoms do not immediately appear...
characterised by chronic
Chronic (medicine)
A chronic disease is a disease or other human health condition that is persistent or long-lasting in nature. The term chronic is usually applied when the course of the disease lasts for more than three months. Common chronic diseases include asthma, cancer, diabetes and HIV/AIDS.In medicine, the...
hives (urticaria) and periodic 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...
, bone pain
Bone pain
Bone pain is a debilitating form of pain emanating from the bone tissue. It occurs as a result of a wide range of diseases and/or physical conditions and may severely impair the quality of life for patients who suffer from it...
and joint pain
Arthralgia
Arthralgia literally means joint pain; it is a symptom of injury, infection, illnesses or an allergic reaction to medication....
(sometimes with joint inflammation
Arthritis
Arthritis is a form of joint disorder that involves inflammation of one or more joints....
), 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...
, 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, swollen lymph glands and enlarged spleen and liver
Hepatosplenomegaly
Hepatosplenomegaly is the simultaneous enlargement of both the liver and the spleen . Hepatosplenomegaly can occur as the result of acute viral hepatitis or infectious mononucleosis, or it can be the sign of a serious and life threatening lysosomal storage disease...
.
The urticarial rash is non-itching in more than half of cases, which is unusual for hives. It is most prominent on the trunk, arms and legs, sparing the palms, soles, head and neck. Associated angioedema
Angioedema
Angioedema or Quincke's edema is the rapid swelling of the dermis, subcutaneous tissue, mucosa and submucosal tissues. It is very similar to urticaria, but urticaria, commonly known as hives, occurs in the upper dermis...
has been reported in a few patients. A review of 94 cases found a mean age at onset of 51 years, and only four patients developed symptoms before the age of 35. The cause and disease mechanism of Schnitzler syndrome remain largely unknown.
Schnitzler syndrome is considered an autoimmune disorder. Chronic hives and a monoclonal gammopathy
Monoclonal gammopathy
Monoclonal gammopathy is a synonym for paraproteinemia.- External links :*...
have been proposed as the major criteria, while the others represent minor criteria.
Diagnosis
Blood testBlood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
s show a high concentration of specific gamma-globulins (monoclonal gammopathy) of the IgM
IGM
IGM as an acronym or abbreviation can refer to:* Immunoglobulin M , the primary antibody against A and B antigens on red blood cells* International Grandmaster, a chess ranking* intergalactic medium* Intragroup medium - see: Intracluster medium...
type. It almost always has light chains
Immunoglobulin light chain
]The immunoglobulin light chain is the small polypeptide subunit of an antibody .A typical antibody is composed of two immunoglobulin heavy chains and two Ig light chains.-In humans:...
of the κ-type. A variant in which IgG is raised has been described, which appears to be ten times as rare. The immunoglobulins may show up in the urine as Bence Jones protein
Bence Jones protein
A Bence Jones protein is a monoclonal globulin protein found in the blood or urine, with a molecular weight of 22-24 kDa.Finding this protein is often suggestive of multiple myeloma or Waldenstrom's macroglobulinemia....
s. Signs of inflammation are often present: these include an increased white blood cell
White blood cell
White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...
count (leukocytosis
Leukocytosis
Leukocytosis is a raised white blood cell count above the normal range in the blood. It is frequently a sign of an inflammatory response, most commonly the result of infection, and is observed in certain parasitic infections...
) and a raised erythrocyte sedimentation rate
Erythrocyte sedimentation rate
The erythrocyte sedimentation rate , also called a sedimentation rate or Biernacki Reaction, is the rate at which red blood cells sediment in a period of 1 hour...
and C-reactive protein
C-reactive protein
C-reactive protein is a protein found in the blood, the levels of which rise in response to inflammation...
. There can be anemia of chronic disease
Anemia of chronic disease
Anemia of chronic disease, also referred to as anemia of inflammatory response is a form of anemia seen in chronic illness, e.g. from chronic infection, chronic immune activation, or malignancy...
. Bone abnormalities can be seen on radiological imaging
Radiology
Radiology is a medical specialty that employs the use of imaging to both diagnose and treat disease visualized within the human body. Radiologists use an array of imaging technologies to diagnose or treat diseases...
(often increased density or osteosclerosis
Osteosclerosis
Osteosclerosis, an elevation in bone density, is normally detected on an X-ray as an area of whiteness, and is where the bone density has significantly increased...
) or biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
.
Because it is such a rare condition (less than 100 cases reported in the literature worldwide before 2008), it is important to rule out other conditions
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...
which can cause periodic fevers, paraproteins or chronic hives. These include (and are not limited to) auto-immune or -inflammatory disorders such as adult-onset Still's disease
Adult-onset Still's disease
Adult-onset Still's disease is a rare form of inflammatory arthritis that was characterized by EG Bywaters in 1971. The underlying cause is unknown. It usually presents with high spiking fevers, joint and muscle pains, a salmon colored rash and other symptoms of systemic inflammation.- History...
, angioedema
Angioedema
Angioedema or Quincke's edema is the rapid swelling of the dermis, subcutaneous tissue, mucosa and submucosal tissues. It is very similar to urticaria, but urticaria, commonly known as hives, occurs in the upper dermis...
, hematological disorders such as lymphoma
Lymphoma
Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
or monoclonal gammopathy of undetermined significance
Monoclonal gammopathy of undetermined significance
Monoclonal gammopathy of undetermined significance , formerly benign monoclonal gammopathy, is a condition in which a paraprotein is found in the blood during standard laboratory tests...
, other causes of hives, cryoglobulinemia
Cryoglobulinemia
Cryoglobulinemia is a medical condition in which the blood contains large amounts of cryoglobulins - proteins that become insoluble at reduced temperatures. Cryoglobulins typically precipitate at temperatures below normal body temperature and will dissolve again if the blood is heated...
, mastocytosis
Mastocytosis
Mastocytosis is a group of rare disorders of both children and adults caused by the presence of too many mast cells and CD34+ mast cell precursors in a person's body.- Classification :Mastocytosis can occur in a variety of forms:...
, chronic neonatal onset multisystem inflammatory disease
Neonatal onset multisystem inflammatory disease
Neonatal onset multisystem inflammatory disease is a rare genetic periodic fever syndrome which causes uncontrolled inflammation in multiple parts of the body starting in the newborn period...
or Muckle-Wells syndrome
Muckle-Wells syndrome
Muckle–Wells syndrome , also known as , is a rare autosomal dominant disease which causes sensorineural deafness, recurrent hives, and can lead to amyloidosis. Individuals with MWS often have episodic fever, chills, and painful joints. As a result, MWS is considered a type of periodic fever syndrome...
.
It is however possible to have more than one rare condition as seen by a patient with Schnitzler's syndrome and cold induced urticaria.
Prognosis
The life span in patients with Schnitzler syndrome has not been shown to differ much from the general population. Careful follow-up is advised, however. A significant proportion of patients develops a lymphoproliferative disorder as a complication, most commonly Waldenström's macroglobulinemia. This may lead to symptoms of hyperviscosity syndromeHyperviscosity syndrome
Hyperviscosity syndrome is a group of symptoms triggered by increase in the viscosity of the blood. Symptoms of high blood viscosity include spontaneous bleeding from mucous membranes, visual disturbances due to retinopathy, and neurologic symptoms ranging from headache and vertigo to seizures and...
. AA amyloidosis
AA amyloidosis
AA amyloidosis is a form of amyloidosis associated with serum amyloid A protein , an acute-phase protein. It causes reactive systemic amyloidosis, as a "reaction" to inflammation, but also familial Mediterranean fever, which is an inheritable condition.-Presentation:The common feature to conditions...
has also been reported in people with Schnitzler syndrome.
Treatment
Antihistamines are not effective in treating the hives in this condition. It may respond to immunosuppressantImmunosuppressant
An immunosuppressant is any substance that performs immunosuppression of the immune system. They may be either exogenous, as immunosuppressive drugs, or endogenous, as ,e. g., testosterone...
drugs such as corticosteroids, cyclooxygenase inhibitors, interferon alpha, interleukin 1 receptor antagonist
Interleukin 1 receptor antagonist
The interleukin-1 receptor antagonist is a protein that in humans is encoded by the IL1RN gene.IL-1RA was initially called the IL-1 inhibitor and was discovered separately in 1984 by two independent laboratories. IL-1RA, is an agent that binds non-productively to the cell surface interleukin-1...
s (Anakinra
Anakinra
Anakinra is a drug used to treat rheumatoid arthritis.-Mechanism:Anakinra is an interleukin-1 receptor antagonist...
), perfloxacin, colchicine
Colchicine
Colchicine is a medication used for gout. It is a toxic natural product and secondary metabolite, originally extracted from plants of the genus Colchicum...
, cyclosporine or thalidomide
Thalidomide
Thalidomide was introduced as a sedative drug in the late 1950s that was typically used to cure morning sickness. In 1961, it was withdrawn due to teratogenicity and neuropathy. There is now a growing clinical interest in thalidomide, and it is introduced as an immunomodulatory agent used...
. The hives may respond to treatment with PUVA
PUVA
PUVA is a psoralen + UVA treatment for eczema, psoriasis, graft-versus-host disease and vitiligo, and mycosis fungoides. The psoralen is applied or taken orally to sensitize the skin, then the skin is exposed to UVA. Long term use has been associated with higher rates of skin cancer.Psoralens are...
, and the bone pain may respond to bisphosphonates.
History
The disease is named after the French dermatologist L. Schnitzler who first described this syndromeSyndrome
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...
in 1972.
See also
- Schinzel-Giedion syndromeSchinzel-Giedion syndromeSchinzel-Giedion syndrome is a congenital neurodegenerative terminal syndrome. First described in 1978 by Dr. Schinzel and Dr. Giedion as a syndrome with severe midface retraction, skull anomalies, renal anomalies and other anomalies...
- List of cutaneous conditions
There is a Facebook page entitled "Schnitzler's syndrome", which has been set up as a forum for support, discussion and sharing experiences and information. It is open access and anybody with an interest in the condition is very welcome to participate.
External links
- http://www.schnitzlersyndrome.com/ - maintained by the University Medical Center St RadboudUniversity Medical Center St RadboudThe Radboud University Nijmegen Medical Centre , is the teaching hospital affiliated with the Radboud University Nijmegen, in the city of Nijmegen in the eastern-central part of The Netherlands....
, Department of General Internal Medicine in Nijmegen, the NetherlandsNetherlandsThe Netherlands is a constituent country of the Kingdom of the Netherlands, located mainly in North-West Europe and with several islands in the Caribbean. Mainland Netherlands borders the North Sea to the north and west, Belgium to the south, and Germany to the east, and shares maritime borders...
.