Skin manifestations of haematological diseases

Author: Dr Sara de Menezes, Basic Physician Trainee, Alfred Health, Melbourne, Australia; Chief Editor: Hon A/Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand, May 2016.


What is haematological disease?

Haematological diseases are a diverse range of conditions affecting the constituents of blood. This includes disorders of the blood cells (red cells, white cells and platelets) and cancerous conditions affecting these blood cells. Skin signs of haematological disease described here are helpful in diagnosis and may also cause complications.

Anaemia

Nutritional anaemia

Anaemia can be the result of nutrient deficiencies, for example iron, B12 or folate.

Skin manifestations are:

  • Pallor of conjunctiva (eyes) and palmar creases
  • Glossitis (smooth red tongue)
  • Poikilodermatous hypopigmentation
  • Hyperpigmentation may be a sign of B12 and folate deficiencies  
  • Brittle nails (koilonychia)
Skin signs of anaemia

Haemolytic anaemia

Haemolytic anaemia, for example due to sickle cell anaemia, results from the destruction of red blood cells, which leads to additional symptoms:

  • Pruritus
  • Jaundice  
  • Petechiae and haemosiderosis (small brown macules)

Myeloproliferative disorders

The process by which blood cells are produced (haematopoiesis) gives rise to cells in either the lymphoid or myeloid lineage.

Polycythaemia

Polycythaemia vera is an example of a chronic myeloproliferative disorder of myeloid cells that results in an increased red cell mass.

Skin manifestations are:

Skin signs of myeloproliferative disease

Mast cell disease 

Mast cell disease (MCD) also arises from a myeloid disorder. In MCD, mast cells accumulate in different organs and tissues in the body.  This can be broadly divided into cutaneous mastocytosis, which is more common in children, and systemic mastocytosis, which is more common in adults.

Skin manifestations are:

  • Maculopapular cutaneous mastocytosis (tan/brown papules in children, reddish-brown macules and papules in adults). Also known as urticaria pigmentosa.
  • Darier sign (erythema and urticaria when affected skin is rubbed)
  • Pruritus
  • Mastocytomas (rare in adults)
Skin signs of mast cell disease

Leukaemia cutis

Leukaemia cutis is a rare manifestation of undiagnosed or previously treated myeloproliferative and lymphoproliferative disorders, eg acute myeloid leukaemia (AML), non-Hodgkin lymphoma. It is a result of infiltration of the skin by leukaemic cells, resulting in variable papules, nodules and plaques. Typically, they can be pinkish, violaceous (purplish) or darker than surrounding normal skin. In addition, they are almost always non-tender and palpable with a firm, indurated texture.

Leukaemia cutis

Lymphoproliferative disorders

Lymphoproliferative disorders arise from disorders of stem cells of the lymphoid lineage. Systemic forms of lymphoma, Hodgkin lymphoma and non-Hodgkin lymphoma, may present with cutaneous signs. Specific cutaneous forms of lymphoma are described here.

Cutaneous T cell lymphoma

Cutaneous T cell lymphoma (CTCL) is a lymphoproliferative disorder that manifests mainly in the skin. The most common form of cutaneous lymphoma is mycosis fungoides.

Skin manifestations

  • Mycosis fungoides: single or multiple well-defined erythematous (red), scaly macules and patches. Varying in size. Lesions can be orange to dusky violet-red
  • Sézary syndrome: erythroderma/ exfoliative dermatitis

Associated features include severe pruritus, hair loss, palmoplantar keratoderma (thickening of the skin of palms of hands/soles of feet) and secondary bacterial infection.

Cutaneous T-cell lymphoma

Cutaneous B cell lymphoma

B cell lymphomas can also present in the skin without evidence of spread elsewhere at the time they are diagnosed. These are known as primary cutaneous B cell lymphomas (PCBCL), including primary cutaneous marginal-zone lymphoma.

One particularly aggressive form of PCBCL is primary cutaneous large B cell lymphoma, leg type. Patients tend to be elderly and present with solitary or clustered, ulcerated, bluish, erythematous plaques or tumours located on the legs. This may be misdiagnosed as leg ulcers related to chronic venous insufficiency.

Cutaneous B-cell lymphoma

Plasma cell and immunoglobulin disorders

Multiple myeloma can rarely present with cutaneous plasmacytoma.

POEMS syndrome presents with Polyneuropathy, Organomegaly, Endocrinopathy, M protein and Skin changes. There is plasma cell proliferation and signs are mediated by overproduction of cytokines and other inflammatory markers.

Cryoglobulins are immunoglobulins that precipitate in cold temperatures. They result in palpable purpura and hyperviscosity syndrome with Raynaud phenomenon. Cryoglobulinaemia is classified as:

  • Type 1 (due to underlying B-cell malignancy)
  • Mixed (Type 1 + Type II) associated with B-cell malignancy or autoimmune diseases

Cold agglutins are cold-sensitive immunoglobulins directed against antigens on red cells. They can lead to Raynaud phenomenon and acrocyanosis.

Skin signs of plasma cell disease

Amyloidosis

Amyloidosis refers to a group of protein-folding disorders where abnormal proteins are deposited in various tissues and organs, including the skin. The commonest of these is AL amyloidosis (light chain).

Skin manifestations

  • Petechiae (pin-point red blood spots)
  • Pinch purpura (blood spots as a result of stroking skin)
  • Ecchymoses (flat bluish/purplish blood spots, larger than petechiae)
  • Waxy induration of skin
  • Macroglossia (enlarged tongue)
Skin signs of amyloidosis

Haematopoietic stem cell transplantation

Stem cells for transplantation can be sourced from the blood, bone marrow or umbilical cord blood. Haematopoietic stem cell transplantation is an option to treat haematological malignancies where other treatment options have failed, for instance diffuse large B cell lymphoma and myeloproliferative disorders.

Complications from haematopoietic stem cell transplantation can arise from side effects of immunosuppression, or from the person’s immune system attacking the ‘foreign’ donated cells (Graft versus Host Disease, GVHD). Any organ in the body can be affected by acute or chronic GVHD (eg liver, lung, joints); however, the skin is most commonly affected.

Skin manifestations

  • Erythema of palms, soles and ears
  • Bullae
  • Eosinophilic folliculitis
  • Poikiloderma (thinning of skin with areas of increased and loss of skin pigment) – chronic GVHD

Extracorporeal photopheresis (ECP) is used to treat cutaneous GVHD in stem cell transplant patients.

Coagulation disorders

Disorders of coagulation result in either excessive blood clotting or excessive bleeding.

Disseminated intravascular coagulation (DIC) results in excessive clotting. It is triggered by severe infection, such as meningococcal disease, or illness, such as disseminated cancer. Severe DIC can consume all the clotting factors, which conversely leads to bleeding.

Skin manifestations are:

  • Petechiae
  • Ecchymoses
  • Bleeding or oozing from wound sites, intravenous lines or catheters

Thrombocytopenia ­leads to a bleeding tendency. For example in immune thrombocytopenia, platelet levels are reduced to a varying degree by circulating antibodies against them.  Thrombocytopaenia can also be due to bone marrow disease, Wiskott Aldrich syndrome and drugs.

Skin manifestations are:

  • Oral or mucocutaneous petechiae
  • Ecchymoses
  • Pigmented purpura

Other coagulation disorders with cutaneous signs include:

  • Antiphospholipid syndrome
  • Warfarin-induced skin necrosis
Skin signs of coagulopathy

Inflammatory disorders associated with haematological disease

Skin manifestations are:

Sweet syndrome (acute febrile neutrophilic dermatosis) is an acute inflammatory skin eruption that is accompanied by fevers and leukocytosis. It can be associated with infections, inflammatory bowel disease, haematological cancers and certain drugs (eg antibiotics). A localised variant of Sweet syndrome is known as neutrophilic dermatosis of the dorsal hands.

Skin manifestations

  • Tender reddish/purplish papules or nodules – can be single or multiple. Lesions may appear bullous, ulcerated or mimic pyoderma gangrenosum
  • Pustules (pus-filled blisters)
  • Tender, erythematous nodules on extremities (can mimic erythema nodosum)
  • Cutaneous pathergy (skin lesions appearing at sites of trauma)
Inflammatory skin disease associated with haematological disease

Adverse reactions to drugs

Drugs used to treat specific haematological conditions can have toxicities that manifest in the skin. Examples include:

Adverse reactions to drugs used in haematology

 

Related Information

References

  • Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J. Harrison’s Principles of Internal Medicine [Internet]. 19th ed. New York: McGraw-Hill; 2016 [cited 2016 April 20]. Available from: Clinician’s Health Channel.  
  • Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffel DJ, Wolff K. Fitzpatrick’s Dermatology in General Medicine. 8th ed. New York: McGraw-Hill; 2012. Chapter 144, Skin Manifestations of Bone Marrow or Blood Chemistry Disorders; p. 1726-1818.  
  • Merola JF. Sweet syndrome (acute febrile neutrophilic dermatosis): Pathogenesis, clinical manifestations, and diagnosis. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on May 14, 2016.)  
  • Negrin RS, Schiffer CA. Interferon alfa for the treatment of chronic myeloid leukemia. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on May 14, 2016.) PubMed.

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