Crow-Fukase Syndrome

Crow-fukase Syndrome
Crow-fukase Syndrome


Crow-Fukase Syndrome is also called POEMS syndrome. POEMS syndrome is a paraneoplastic syndrome whose acronym stands for less than half of the defining features of the disease, that is, polyradiculoneuropathy, organomegaly, potentially including coexisting Castleman disease, endocrinopathy, monoclonal plasma cell neoplasm, and skin changes. The other important features include papilledema, extravascular volume overload, sclerotic bone lesions, thrombocytosis, elevated VEGF, and abnormal pulmonary function. The diagnosis is based on having both the polyradiculoneuropathy and the monoclonal plasma cell disorder, and at least 1 of the other 3 major criteria (Castleman disease, sclerotic bone lesions, or elevated VEGF) and at least one minor criterion. The diagnosis is often delayed with intervening incorrect diagnoses of chronic inflammatory demyelinating polyradiculoneuropathy, myeloproliferative disorder, and monoclonal gammopathy of undetermined significance. Prompt treatment directed at the underlying plasma cell clone produces dramatic responses in the majority of patients. Although there are no randomized clinical trial data to direct the best therapy, for patients with disseminated disease, high-dose chemotherapy with peripheral blood transplantation has yielded durable benefit, whereas radiation therapy is typically effective for patients with a more localized presentation. More universal recognition of and more scientific inquiry into the underpinnings of the disease will provide direction toward the best treatment strategies in the future.


The cause of POEMS syndrome is not well understood. POEMS syndrome is a paraneoplastic disorder, which means that the signs and symptoms of the syndrome appear as a manifestation of the plasma cell disorder that the patient has (most patients are seen with osteosclerotic myeloma or monoclonal gammopathy of unknown significance); however, the mechanism by which this occurs is unknown. It is associated with a chronic overproduction of some substances known as pro-inflammatory cytokines (small molecules that act as messengers between cells to promote inflammation). These include interleukins (IL-1b, IL6) which are cytokines that help regulate immune responses, TNFα (Tumor Necrosis Factor alfa is a cytokine which is involved in the inflammatory process), and vascular endothelial growth factor (VEGF – a powerful vasodilator that may cause leaky blood vessels) which seem to be important in this disorder.


POEMS syndrome is a rare, multisystem disorder. POEMS stands for the disorder’s features, which may include Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes. Signs and symptoms may include progressive sensorimotor polyneuropathy; enlarged liver, spleen, and/or lymph nodes; a disorder of the endocrine glands (often with multiple abnormalities); a monoclonal plasma cell proliferative disorder; and darkening of the skin (hyperpigmentation). Various other symptoms may also occur and may vary among affected people. The underlying cause of the disorder is not well understood. POEMS syndrome is a chronic disorder, with a median survival time of 8-14 years. There is no standard treatment; management depends on the underlying plasma cell disorder and may include radiation therapy, chemotherapy, and/or hematopoietic cell transplantation.


Treatment of the POEMS syndrome can be broken down into 2 major categories: targeting the underlying clone and targeting the rest of the syndrome. Both are important to achieve the best outcomes. Monitoring for hematologic response is a challenge because the serum M-protein is typically small making standard multiple myeloma response criteria inapplicable in most cases. In addition, patients can derive substantial clinical benefit, even in the absence of an M-protein response.38,39 In addition, although the immunoglobulin free light chains are elevated in 90% of POEMS patients, the ratio is normal in all but 18%,40 making the test of limited value for patients with POEMS syndrome. Following VEGF is rather straightforward, but one must be cognizant that spurious VEGF levels do occur. Following the other features of the syndrome is also challenging because there are more than 2 dozen parameters that could be assessed in a given patient with POEMS syndrome, given the multisystem nature of the disease focus on features that were present at baseline and follow each abnormality at each visit or at every other visit.



People who are suspected of having POEMS syndrome should first have their medical history evaluated and undergo a complete physical exam. Features suggestive of POEMS syndrome in the history include complaints of neurological symptoms, skin changes, signs of extravascular volume overload, and symptoms suggestive of an endocrine disorder (such as gynecomastia or irregular periods). A detailed physical exam should include an eye exam for papilledema; a neurologic exam; evaluation for enlargement of organs (organomegaly); examination of the skin; and evaluation for the presence of peripheral edema (swelling due to fluid accumulation), pleural or pericardial effusion (fluid build-up around the lungs or heart), ascites, clubbing (enlargement of the fingertips), heart failure, and cardiomyopathy.

A diagnosis of POEMS syndrome requires both the presence of polyneuropathy and a monoclonal plasma cell proliferative disorder, plus the presence of at least one major and one minor criterion on a physical exam, imaging, or laboratory evaluation.

Major criteria include:

● An osteosclerotic or mixed sclerotic/lytic lesion seen on plain films or CT scan measuring at least 0.8 cm in the longest dimension

● Castleman’s disease

● Elevated serum or plasma vascular endothelial growth factor (VEGF) levels at least 3 to 4 times the upper limit of normal

Minor criteria include:

● Organomegaly (enlargement of the spleen, liver, or lymph nodes)

● Extravascular volume overload (peripheral edema, ascites, or pleural effusion)

● Endocrinopathy (excluding diabetes mellitus or hypothyroidism)

● Skin changes

● Papilledema

● Thrombocytosis or polycythemia

Many affected people are initially misdiagnosed as having other disorders, such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). In addition, a number of conditions are associated with a plasma cell disorder and polyneuropathy (with or without osteosclerotic bone lesions) and need to be distinguished from POEMS syndrome.