Cutaneous Manifestations of Hematological Disorders: A Detailed Glossary

Introduction

Hematology is the study of blood and blood constituents. Any abnormalities in the constituents can give rise to different disorders. Hematological disorders can be those that affect the count of blood cells or any cancerous changes. Some of these conditions have cutaneous manifestations. In some cases, the medications given to treat such disorders can cause skin changes.

What Is a Hematological Disease?

Hematological disorders are any condition that affects the constituents of blood. Therefore, it includes diseases that involve blood cells such as white blood cells, red blood cells, and platelets; and cancerous conditions affecting these blood cells. Some hematological disorders have skin manifestations, which can help to diagnose the conditions, in some cases, may cause complications.

What Are the Various Hematological Diseases With Cutaneous Manifestations?

1. Anemia:

Nutritional Anemia:

Anemia occurs as a result of nutritional deficiencies such as B12 or folate. Skin manifestations include:

• Glossitis: smooth red tongue.

• The pallor of eyes (conjunctiva).

• Palmar creases.

• Hyperpigmentation.

• Poikilodermatous hypopigmentation.

• Brittle nails and koilonychia.

Hemolytic Anemia:

Hemolytic anemia occurs when the red blood cells are destroyed more than their production. Hemolysis or destruction of red blood cells. Skin manifestations include:

• Jaundice or yellow skin and eyes.

• Pruritus.

• Hemosiderosis which are small brown discoloration on the skin

• Petechiae: red spots on the skin.

2. Myeloproliferative Disorders:

Hematopoiesis is the process of production of blood cells. Sometimes there is an increase or decrease in the production of white blood cells, which can cause disorders such as:

Polycythaemia:

Polycythaemia vera is a chronic myeloproliferative disorder that results in an increase in the number of red blood cells.

Skin features include:

• Aquagenic pruritus is itching that gets triggered by contact with water.

• Erythromelalgia is the burning and redness of hands or feet.

• Plethora, or ruddy cyanosis, is a florid complexion.

• Acrocyanosis is the bluish-purplish discoloration of hands or feet.

• Livedo reticularis is lace-like purplish discoloration.

• Pyoderma gangrenosum or ulcers.

Mast Cell Disease:

Mast cell disease arises due to myeloid disorder, which causes mast cells to accumulate in different organs and tissues in the body. This can be of two types:

1. Cutaneous mastocytosis is found in children.

2. Systemic mastocytosis is more common in adults.

Clinical manifestations involving skin include:

• Mastocytomas (tumor of mast cells-a type of immune cell).

• Pruritus.

• Darier sign (red hives produced after scratching).

• Maculopapular cutaneous mastocytosis, also known as urticaria pigmentosa. It is brown papules or discoloration of the skin in children and reddish-brown macules and papules in adults.

VEXAS Syndrome:

It is a genetic condition generally seen in middle-aged men. It is characterized by myelodysplastic hematological disorders (clonal proliferation of abnormal hematopoietic or blood-forming cells) and autoinflammatory features.

Leukemia Cutis:

A rare manifestation of previously treated or undiagnosed myeloproliferative and lymphoproliferative disorders. Examples include non-Hodgkin lymphoma and acute myeloid leukemia. Various papules, plaques, and nodules form in the skin due to the infiltration of leukemic cells into the skin. They appear as pinkish-purplish areas. They can be palpated but non-tender and indurated in texture.

3. Lymphoproliferative Disorders:

These are disorders that arise from stem cells of lymphoid origin. Hodgkin lymphoma, systemic forms of lymphoma, and non-Hodgkin lymphoma may have cutaneous signs. Some cutaneous manifestations include:

Cutaneous T-cell Lymphoma:

CTCL, or cutaneous T-cell lymphoma, has many cutaneous manifestations. Mycosis fungoides is the most common form of cutaneous lymphoma.

Skin Manifestations:

• Sezary syndrome: exfoliative dermatitis or erythroderma.

• Mycosis fungoides: scaly patches, tumors, or plaques that are single or multiple in number. They vary in size. Lesions are orange to violet-red in color or sometimes hypopigmented.

• Pruritus, palmoplantar keratoderma, hair loss, and secondary bacterial infection are associated features present. Thickening of the skin of the soles or hands is called palmoplantar keratoderma.

Cutaneous B-cell Lymphoma:

• There can be skin manifestations of B-cell lymphomas; they can appear without evidence of spread anywhere in the body. These are called primary cutaneous B-cell lymphomas (PCBCL). Some of them are associated with the Epstein-Barr virus.

• Primary cutaneous large B-cell lymphoma, leg type, is the aggressive form of PCBCL. These patients are generally elderly, and skin manifestations include ulcerated, bluish, solitary, or clustered red (erythematous) tumors or plaques found on the legs. They can be confused with leg ulcers that arise due to venous insufficiency.

4. Amyloidosis:

A group of protein disorders where abnormal protein is deposited in tissues and organs, including the skin, is known as amyloidosis. AL amyloidosis (light chain) is the most common among these.

Cutaneous manifestations include:

• Pinch purpura, red discoloration on stroking the skin.

• Petechiae: pinpoint red spots.

• Waxy induration on the skin.

• Ecchymoses: purplish-bluish discoloration.

• Macroglossia (tongue larger than normal).

5. Plasma Cell and Immunoglobulin Disorders:

• The cutaneous presentation of multiple myeloma is plasmacytoma.

• Polyneuropathy (malfunction of peripheral nerves), organomegaly (organ enlargement), endocrinopathy (endocrine gland pathology), M-protein, and skin changes are also known as POEMS syndrome. Overproduction of inflammatory markers and cytokines can be seen.

• Purpura which is palpable, and the Raynaud phenomenon occur as a result of cryoglobulins. Cryoglobulins are immunoglobulins that precipitate in cold temperatures.

• Cold agglutinin can lead to acrocyanosis and Raynaud's phenomenon. Cold agglutinin is an immunoglobulin that is cold-sensitive and directed against antigens on red blood cells.

6. Hematopoietic Stem Cell Transplantation:

• Stem cells are cells that have the potency to differentiate into any type of cell. They can be sourced from bone marrow, blood, or umbilical cord. Stem cell transplantation can be done in cases where other treatment options have failed, such as in myeloproliferative disorders and B-cell lymphoma.

• But this transplantation can cause side effects of immunosuppression or graft rejection by the body's immune system (graft versus host reaction). This can affect organs such as the lungs, liver, joints, and, most importantly, the skin.

• Bullae (large fluid-filled blisters on the skin).

• Erythema of palms, ears, and soles.

• Poikiloderma is the thinning of the skin with loss of skin pigmentation.

• Eosinophilic folliculitis (a recurrent skin disorder).

• Cutaneous disorders of graft versus host disease stemming from stem cell transplant can be treated by extracorporeal photopheresis (ECP).

7. Coagulation Disorders:

Blood has many factors that enable coagulation while bleeding and prevent it otherwise. Disturbance in coagulation factors can result in excessive bleeding or excessive blood clotting.

Disseminated intravascular coagulation (DIC) can result in excessive clotting. Meningococcal disease or cancer can lead to DIC consuming all clotting factors, which can lead to bleeding.

Skin signs include:

• Ecchymoses.

• Petechiae.

• Bleeding from wound sites, catheters, or intravenous lines.

8. Thrombocytopenia:

Platelet count disorder can lead to bleeding of varying degrees. Wiskott-Aldrich syndrome, certain drugs, or immune thrombocytopenia can be some of the causes of platelet disorders.

Cutaneous manifestations include:

• Ecchymoses.

• Skin and oral petechiae.

• Pigmented purpura.

• Other clotting disorders include

• Blue toe syndrome.

• Warfarin-induced skin necrosis.

• Antiphospholipid syndrome.

9. Adverse Reactions to Drugs:

Some drugs that are used to treat hematological conditions can have a toxic reaction that can give rise to skin conditions such as:

• Porphyria cutanea tarda and vitiligo: which is caused by interferon-alpha used in the treatment of chronic myeloid leukemia.

• Hydroxyurea can lead to actinic keratoses, squamous cell carcinoma, dry skin, leg ulcers, nail changes, and hyperpigmentation.

• Imatinib used to treat CML can cause psoriasiform dermatitis, alopecia, pruritus, and photosensitivity.

Conclusion

Hematological disorders can be problems in the blood constituents, increase or decrease in their count, it can be cancers: or coagulation disorders. Some of these can cause skin changes. In some cases, medications given to treat these can cause skin reactions. Treatment varies depending on the cause of the skin manifestation. In most cases, skin manifestation resolves by solving the underlying cause.