Leukemia is an uncontrollable proliferation of white blood cells due to an abnormality in the bone marrow. It is also known as cancer of the white blood cells. When there is abnormal production of the white blood cells (leukocytes) they proliferate too much and are everywhere. Some of these cells infiltrate into layers of the skin, either the epidermis, dermis or the subcutaneous tissue. This infiltration of white blood cells in the skin results in variable cutaneous lesions. This pathology is called Leukemia cutis.
These lesions can be papules or nodules, but they can also be filled with skin cells and look harder. The term leukemia is used in a broader aspect, but when we look at it more deeply there are different types depending on the precursor cells involved. The infiltrated cells can be members of the myeloid series or the lymphoid series, and leukemia cutis is commonly seen at a late phase of the disease, as a manifestation of the systemic nature of leukemia. Leukemia cutis has got a poor prognosis, usually because it manifests at the last stage of a systemic leukemia and occurs along with involvement of other organs as well, where infiltration of leukocytes has taken place.
Signs and symptoms
Leukemia cutis is a manifestation of leukemia. Thus, the majority of symptoms are the same, except for the skin changes. Patients with leukemia may report the symptoms listed below. In the list, you will also find the characteristic features of leukemia cutis lesions explained in detail:
- Bleeding from the gums
- Bone and joint pain
- Fever
- Frequent infections
- Frequent or severe nosebleeds
- Lumps caused by swollen lymph nodes in and around the neck, underarm, abdomen or groin
- Pale skin
- Shortness of breath
- Weakness, fatigue or a general decrease in energy
- CNS involvement- seizures, facial nerve palsies.
- Hepatosplenomegaly
Skin Lesions
In most cases, skin lesions of leukemia cutis are not symptomatic. They are not itchy or painful at all. They usually appear in the area if the head, neck or trunk, especially when there’s a scar or injury around. Most lesions look like nodules and papules with a variable color ranging from red to brown. Some patients may have a lesion that breaks and becomes an open wound that won’t heal, also known as ulcer. In this case, the lesion can start displaying symptoms. Other symptoms that may guide the diagnosis of leukemia cutis are as follows:
- Pin point bleeding under the skin
- Ulcers and Blisters
- Gum bruising
- Blueberry muffin syndrome in children (Blueish of violet spots in the skin)
- Other unusual manifestations include: erythema nodosum, pyoderma gangrenosum, skin lesions like urticaria.
Why does it happen?
The cause of leukemia cutis includes both genetic and environmental factors. Both of these factors in the end result in chromosome changes and alterations in the locations of the genes. In some cases, having a disease that features chromosome alterations may cause an increased incidence of leukemia cutis. For example:
- Down syndrome: It is also known as trisomy 21 because there is an extra copy of chromosome number 21. This alteration causes specific facial features, mental retardation and growth retardation. Recent studies show that the mutations that cause down syndrome are responsible for causing leukemia as well.
- Bloom syndrome: It is a rare recessive disorder due to a defect in the BLM gene. It is characterized by short stature, photosensitive changes of the skin and a strong predisposition for the development of cancer. The mutation in the BLM gene causes other cells to have an abnormal break in the chromosomes, when it involves the bone marrow it can cause Leukemia as well.
- Klinefelter syndrome: It is due to 2 or more X- Chromosomes in males, resulting in infertility and poor functioning testicles. It is due to an error in cell division and can lead to leukemia as well.
- Wiskott-Aldrich syndrome: An X-linked recessive disease characterized by bloody diarrhea, decreased platelet count, immune deficiency and eczema. These patients have a potential risk to develop leukemia.
- Fanconi Anemia: A rare inherited bone marrow failure syndrome which has a higher risk for getting Leukemia and then leukemia cutis.
Apart from these, there are types of leukemia with familial predisposition to suffer the disease. Other causes include acquired (not congenital) genetic mutations which result in a variation in the symmetry of the stem cells from which these leukocytes come from. These mutations in the end result in a defective stem cell, a proliferation of a subgroup of cells, which then start to infiltrate into the epidermis, dermis or subcutaneous layer and keep on proliferating there.
Risk factors
The environmental factors that can increase the incidence of Leukemia cutis include:
- Benzene exposure: Benzene is carcinogenic to human cells and it can cause leukemia.
- Ionizing radiation: The bone marrow from where the blood cells are produced is sensitive to radiations. They can suppress the maturation process and can cause leukemia.
- Viral infections: Especially the Epstein Bar virus (EBV), Cytomegalovirus (CMV), Varicella zoster virus (VZV) and Human herpes virus (HHV). They have been associated with the development of different types of leukemia.
- Chemotherapy induced leukemia: Alkylating agents used for the treatment of other cancers can result in bone marrow suppression and can cause leukemia.
- Hematologic disorders: Such as Myelodysplastic syndrome, in which all the blood cells do not mature properly and can be one of the cause of leukemia cutis.
All of these factors, whether genetic or environmental in the end will cause an arrest in the maturation of the leukocyte precursor cells, the proliferation of immature leukocytes, which will continue to reach the layers of the skin and deposit, causing abnormal lesions.
Treatment options
There is no direct treatment for leukemia cutis, but it is important to treat the underlying type of leukemia and the cause. Most of the causes of leukemia are genetic and cannot be corrected, but the progression of the disease can be stopped by various methods. A medical oncologist has to take the decision after all of his investigations are carried out and the type of leukemia is identified. The treatment options for leukemia typically include systemic chemotherapy, which is the first choice depending on the stage of the cancer. Other treatment options include localized radiation, photo therapy and electron beam therapy.
If the underlying cause is a viral infection, the patient should be given prophylactic doses of antivirals before going for systemic chemotherapy. Patients undergoing chemotherapy can usually have lesions and ulcers in the mouth and gums as a side effect of chemotherapy drugs, and in such cases mouth wash and ketoconazole cream can be used to treat the symptoms.
For the treatment of leukemia cutis, radiotherapy can be an option. It can be used to deal with the pain and pruritus caused by the lesions, and when patients are not eligible for systemic chemotherapy. Nowadays, several advancements are made to treat patients with leukemia cutis through methods such as Helical irradiation of the total skin (HITS) therapy or helical arc radiotherapy of total skin (HEARTS), used to treat someone with leukemia cutis.
The drugs used in chemotherapy are Anti neoplastic agents which cause the inhibition of proliferation of the problem cell. Some of these drugs include Daunorubicin, cytarabine, idarubicin and methotrexate.
Recommendations
Recommendations for patients with leukemia cutis are made by an oncologist after the investigations and clinical features confirm it as a type of leukemia and after staging. Some of the precautionary measures that should be taken into consideration include the following:
- The patient should avoid any kind of strenuous activity and going to public places to reduce the risk of infections.
- They should avoid contact with hospitalized individuals and those who are recently vaccinated
- Patient with decreased white cell count should eat well-cooked foods and avoid fresh fruits and vegetables.
- Newly diagnosed patients should follow up on routine basis and consult their healthcare provider about the progression of the disease.
- Patients with leukemia cutis might have a difficulty in getting their IV lines passed because of the bruises. In these cases, it might be a better option to pass a central venous line for chemotherapy.
- Leukemia resulting from infective agents such as virus and fungi is controlled with antivirals. In these cases, it is paramount that patients take the antiviral or antifungal medications as instructed.
Conclusion
Leukemia cutis is a complication of leukemia in which there is excessive proliferation of white blood cells which start depositing in the layers of the skin. It is a rare condition and can manifest with any type of leukemia, no matter what the cause is. To treat leukemia cutis, it is important to stop the progression of leukemia first. Leukemia cutis patients present with abnormal skin lesions ranging from papules, plaques, nodules to ulcers. These lesions mostly occur at sites of previous injury or in the area of previous scars.
References
Cho-Vega, J. H., Medeiros, L. J., Prieto, V. G., & Vega, F. (2008). Leukemia cutis. American Journal of Clinical Pathology, 129(1), 130-142.
Resnik, K. S., & Brod, B. B. (1993). Leukemia cutis in congenital leukemia: analysis and review of the world literature with report of an additional case. Archives of dermatology, 129(10), 1301-1306.
Wagner, G., Fenchel, K., Back, W., Schulz, A., & Sachse, M. M. (2012). Leukemia cutis–epidemiology, clinical presentation, and differential diagnoses. JDDG: Journal der Deutschen Dermatologischen Gesellschaft, 10(1), 27-36.