Chédiak-Higashi-Steinbrinck syndrome (CHS) in a 27-year-old woman - effects of G-CSF treatment

Abstract

Chédiak-Higashi-Steinbrinck syndrome (CHS) is a rare autosomal recessive disorder which is usually lethal in early childhood. Diagnostic hallmark is the occurrence of giant inclusion bodies in peripheral leukocytes and their bone marrow precursors. We report on a 27-year-old female patient who was admitted for treatment of a skin abscess. She recovered after intravenous antibiotic treatment and surgical incision. Hematological investigation was initiated because of a persisting neutropenia of 15%, with a leukocyte count initially in the normal range but subsequent leukopenia. Case history revealed recurrent skin infections from childhood on, regularly requiring surgical intervention. One year prior to admission a neuropathy had been diagnosed, while a partial albinism had been known for years. Microscopic examinations of peripheral blood and bone marrow aspirate smears were diagnostic for CHS. Additionally, a secondary antibody deficiency was found. Normalization of the white blood cell count, including the differential count, was observed following initiation of G-CSF treatment. Functional assessment of phagocytosis and oxidative burst activity of granulocytes revealed normal results before and after stimulation with G-CSF, however, natural killer cell activity was only weak, with slight improvement after G-CSF treatment in vivo. Cytogenetic analysis showed a normal female karyotype. Although the haploidentical brother of the patient may serve as an allogeneic stem cell donor, transplantation has been postponed because of further deterioration of her already existing CHS-specific neurological impairment. Nevertheless, while receiving G-CSF maintenance treatment our patient experienced no further infectious episodes within 6 months after diagnosis of CHS.

Infections in Patients with Inherited Defects in Phagocytic Function

“…Infections usually involve the skin and respiratory system and include cellulitis, abscess, otitis media, pneumonias, pyoderma, and periodontal disease. Skin abscesses can be particularly problematic, requiring frequent surgical intervention (24). Infections with S. aureus are common.…”

Das Chediak-Higashi-Syndrom

“…Spinale MRT-Aufnahmen, die bisher bei drei berichteten adulten CHS-Patienten angefertigt wurden, machten in zwei Fäl-len eine Atrophie des Rückenmarks deutlich [2,29]. Bis auf eine leichte Eiweißer-höhung waren Liquoruntersuchungen bei neurologisch auffälligen adulten CHS-Patienten ohne pathologischen Befund [22,24,26,29].…”

“…Als zusätzliche Behandlungsoption können granulozytenstimulierende Faktoren ("granulocyte-colony stimulating factor", G-CSF) zu einer Verbesserung der Leukozytenfunktion führen [2].…”

“…Nach vorübergehender Besserung der hä-matologischen Störungen war es nachfolgend zu einer Transplantatabstoßung gekommen. Seit Diagnosestellung war die Patientin mit granulozytenstimulierenden Faktoren behandelt worden [2].…”

Analysis of the Lysosomal Storage Disease Chediak–Higashi Syndrome

“…The only therapeutic intervention is a bone marrow transplant. Replacing the hematopoetic system eliminates both bacterial infections and the accelerated phase [6,7]. Patients who have either had transplants or have managed to not get the accelerated phase show a progressive neuropathy.…”