Dual Challenges: Case Comparison of Children with Ichthyosis and Acute Leukemia
Authors: Czogala Wojciech , Zurek Kacper Szczepan , Waliszczak Grzegorz , Czogala Malgorzata , Szczepanski Tomasz , Skoczen Szymon 
Published: December 2024

The coexistence of severe chronic diseases and acute leukemia can be a diagnostic and treatment challenge It requires a complex medical approach that includes not only precise diagnosis and treatment of both diseases, but also management of their mutual interactions. The presented cases show the possible impact of various genetic mutations of ichtyosis - related genes on the therapeutic process in acute lymphoblastic leukemia (ALL).

The cases we compare have different genetic origins of ichthyosis: the first boy has a germline mutation of the SPINK5 gene (p.Cys510*)- Netherton syndrome, while the second has a mutation of the STS gene (p.Ala364Pro)- X-linked recessive ichthyosis (RXLI). It is worth emphasizing that in the second boy it is the first such mutation of the STS gene in the literature. The boys were diagnoses with leukemia at different ages (15 years vs. 2.5 years). The final diagnoses were: for the first boy - ALL, common type, L1 (45, XY, t(5; 18) (q35 ;q21), del(12)(pI3), -13 ,der(21 )add(21) (q22)[ 18]/46, XY, ETV6/RUNX1 fusion) and for the second boy - B-ALL, common type (karyotype 46,XY, JAK2 p.Arg683Gly, IL17RC p.Ala303Thr, NUP214 p.Arg815Gln).The first patient underwent therapy according to ALL IC-BFM 2009 HRG protocol (initial WBC 4.420/ul, CNS 3, 15th day MRD 11%, 33th day MRD neg) while the second boy was treated according to the ALL IC 2009 IRG protocol (initial WBC- 22.970/ul, CNS 1, 15th day MRD neg, 33th day MRD neg). The course of the diseases differed - the first suffered many notable complications during chemotherapy, mainly due to infections such as EBV, sinusitis, or multiple skin infections. Complications were worsened by chemotherapy including Mtx (dermatitis WHO grade IV), glucocorticoid-induced diabetes, hepatotoxicity, syndrome of inappropriate antidiuretic hormone secretion (SIADH).

The second boy, on the other hand, developed complications typical for chemotherapy: severe thrombopenia requiring FFP and platelet transfusions, frequent upper respiratory tract infections, secondary immunodeficiency and glucocorticoid-induced Cushing's syndrome.

The reason for the increased number of recorded infectious complications in the first boy was probably related to the Netherton syndrome (significant skin and mucosal barrier disruption, T and B lymphocyte maturation disorder, reduced cytotoxicity, defective thymic differentiation). The severity of skin lesions in both cases could also play a significant role. Both boys are currently in complete remission for 7 and 6 year.

In available literature, only a few cases of X-linked ichtyosis complicated with ALL were reported, with no detailed genetic analysis. There might be no direct interplay between the mentioned mutations, however, some postulate that increased chromosome fragility of lymphocytes in ichtyosis may lead to higher incidence of leukemia in affected population. The similar pathogenesis is proposed in Netherton syndrome. Clot formation abnormalities were are more frequent in X-linked ichtyosis with higher predisposition to haemorrhagic complications.

The described cases offer an important addition to the accumulated knowledge on the purported correlations between ichtyosis and leukemia and highlight the need for deeper molecular studies in patients with ichtyosis.