Acute myeloid leukaemia and skin C92.0

Acute myeloid leukemia (AML) is a neoplasm of myelopoiesis with variable involvement of myeloid cell lineages. Untreated AML leads to death in 50% of patients 5 months after the first symptoms (Southam CM et al 1951). It was only after the introduction of daunorubicin and cytarabine that complete remissions and long-term success were achieved (Crowther D et al 1970).The prognosis of AML has improved steadily since the 1970s. Prognosis of older patients over 70 to 75 years of age remains poor.

Skin/mucosal manifestations in acute myeloid leukemia can be divided into:

• Specific leukemic skin infiltrates (leukaemia cutis).
• Non-specific skin reactions (symptoms due to cytopenia)
• Immunological skin reactions
• Drug-induced skin reactions

Origin is the pathological proliferation of clonal myeloid cells, mostly belonging to the highly proliferative progenitor pool (i.e. CD34+/CD38+) or more rarely to the stem cell pool (i.e. CD34+/CD38-). This proliferating clone overgrows the healthy bone marrow and leads to depletion of healthy hematopoiesis with the resulting clinical consequences:

• Granulocytopenia (infections, sepsis)
• Thrombocytopenia (bleeding)
• Anemia (dyspnea, reduced performance).

Specific leukaemic skin infiltrates(leukaemia cutis): Specific leukaemic skin infiltrates and gingival hyperplasia as signs of extramedullary manifestation are mainly found in myelomonocytic/monoblast differentiated AML (Parsi M et al. 2021). Leukaemia cutis is the cutaneous manifestation of any type of leukemia and occurs in 10 to 15% of patients with AML. Very rarely, the cutaneous infiltrates of AML precede bone marrow or peripheral blood involvement (aleukemia cutis).

urticarial lesions have also been described, which are usually misdiagnosed clinically and histomorphologically as leukocytoclastic vasculitis (Scott AD et al. 2015).

Facies leonina: thickening of the facial skin due to specific infiltration.

Unspecific skin reactions (symptoms due to cytopenia).

• Epistatxis
• Petechiae
• Ecchymoses

Immunological skin reactions

• Sweet's syndrome (Merlant M et al. (2021)
• Eosinophilic fasciitis (Haddad H et al 2014).

Signs of decreased immune defenses

Cutaneous/mucosal signs of decreased immune defenses are not infrequently detectable:

• Candida infections
• Pyoderma: atypical, therapy-resistant pyoderma, even foudroyant (sepsis).
• Ecthyma gangrenosum (Koumaki D et al 2019).
• Pyoderma gangraenosum, also bullous variants (Lamet S et al. 2010)

Therapy-induced skin manifestations

• Varicella zoster reactivations during cytostatic therapy (Vermont CL et al 2014).
• Other cytostatic-induced skin changes depending on drug
• Eruption of lymphocyte recovery(ELR) an "immune reconstitution syndrome" that can occur 1-2 weeks after after aggressive chemotherapy (Hurabielle Cet al 2018).

1. Parsi M et al (2021) Leukemia Cutis. 2021 Jul 21. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. PMID: 31082180.
2. Perl AE et al (2019) Gilteritinib or chemotherapy for relapsed or refractory FLT3-mutated AML. N Engl J Med 381:1728-1740.
3. Scott AD et al (2015) Acute generalized exanthematous pustulosis (AGEP) secondary to imatinib in a patient with chronic myeloid leukaemia. Clin Exp Dermatol 40:926-927

4. Hurabielle Cet al (2018) Eruption of lymphocyte recovery with atypical lymphocytes mimicking a primary cutaneous T-cell lymphoma: a series of 12 patients. Hum Pathol71:100-108.

5. Southam CM et al. (1951) A study of the natural history of acute leukemia with special reference to the duration of the disease and the occurrence of remissions. Cancer January: 39-59.
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7. Vermont CL et al (2014) Varicella zoster reactivation after hematopoietic stem cell transplant in children is strongly correlated with leukemia treatment and suppression of host T-lymphocyte immunity. Transpl Infect Dis 16: 188-194.
8. Weinberg OK et al. (2009) Clinical characterization of acute myeloid leukemia with myelodysplasia-related changes as defined by the 2008 WHO classification system. Blood 113:1906-1908.