syndromes associated with plasma cell disorders

N.B. Not a comprehensive list and unlikely to feature in FRCPath as several are vanishingly rare. Myeloma, plasmacytomas and MGUS of course have their own pages.

POEMS

(Rare, est. 0.3/100,000)

Synonyms

Osteosclerotic myeloma, Takatsuki Syndrome, Cro-Fukase Syndrome

Cause

Uncertain, but elevated VEGF (Vascular endothelial growth factor) usually present

Almost always lambda light chain restricted plasma cells

Presentation

Adult onset

Multisytem, paraneoplastic disorder, POEMS:

  • Polyneuropathy (sensorimotor, peripheral)

  • Organomegaly (liver/spleen/lymph nodes)

  • Endocrinopathy (any)

  • Monoclonal plasma cell disorder

  • Skin changes (particularly hyperpigmentation, skin thickening, hypertrichosis)

Although not in acronym, the followin are important additional features:

  • Fluid overload

  • Optic nerve oedema

  • Osteosclerotic bone lesions

  • Thrombocytosis

  • Thrombosis

May also be associated with Castleman disease

Diagnosis

Does not require all of the above

How I treat suggests demyelinating neuropathy plus any of thrombocytosis, oedema, papilloedema is most suspicious of a diagnosis of POEMS

Lambda light chain usually elevated (but with a normal K:L ratio in up to 80%!)

Treatment

Address individual complications

Anti-myeloma therapy (systemic or radiotherapy to osteosclerotic lesions)

Symptoms may improve despite minimal change in light chains

References

How I treat 2012, Rare Diseases Database

TEMPI

(<30 ppl worldwide in 2019)

Presentation

Adult onset

TEMPI

  • Telangectasia (face, trunk and arms)

  • Erythrocytosis w/ Elevated erythropoietin (JAK2 negative)

  • Monoclonal gammopathy (<10% PC in BM)

  • Perinephric fluid collections

  • Intrapulmonary shunting (—> progressive hypoxia)

Other reported features include intracranial haemorrhage, facial erythema, thrombosis

Treatment

Case reports of rapid, complete responses to bortezomib-based therapy

References

Blood 2020, GARD website, NEJM First case series 2011

AESOP

(only 18 reported cases in 2021)

AESOP - Adenopathy and extensive skin path overlying a plasmacytoma

Red-Brown violaceous skin occuring as the presenting feature at the site overlying a plasmacytoma

Presentation also associated with lymphadenopathy and wide-ranging polyneuropathies

Can be considered as an early presentation of POEMS

Treated as per plasmacytomas

References

J Clin Aesthet Dermatol 2012, Clinics in Dermatology 2021

schnitzler Syndrome

(160 reported cases)

IgM paraprotein with a chronic red rash similar to urticaria

Associated symptoms include recurrent episodes of lymphadenopathy, fever, arthritis, bone pain

Poorly defined but probably a paraneoplastic autoinflammatory condition

Treatment - symptomatic, immune suppression, IL-1 inhib and surveillance for subsequent Waldenstroms

References

NORD website, Blood 2018, J Haem 2021

CANOMAD

(largest case series is 45 patients)

Adult onset

CANOMAD

  • Chronic Ataxic Neuropathy

  • Ophthalmoplegia

  • IgM paraprotein

  • Cold Agglutinins

  • Anti-Disialosyl antibodies

Treatment

IVIg and rituximab have reported 50% response rates

Poor response to steroids

Surveillance for Waldenstroms

References

GARD website, Blood 2020