Introduction
The “hair-on-end” appearance of the skull is a striking radiologic finding, most commonly associated with severe forms of hemolytic anemias such as thalassemia major. This sign is characterized by vertical striations on skull radiographs resembling hair standing on end, reflecting compensatory bone marrow expansion. In this column, we will explore the etiology, pathophysiology, epidemiology, clinical presentation, imaging features, treatment, and prognosis of the hair-on-end skull, using the attached case study of a 24-year-old male with severe thalassemia major.
Etiology and Cause
The hair-on-end skull is caused by bone marrow hyperplasia due to chronic hemolytic anemia. The continuous destruction of red blood cells in thalassemia stimulates the bone marrow to produce more erythroid cells. To meet this demand, bone marrow expands into the diploic spaces of the skull, leading to:
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Widening of the diploic space.
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Thinning of the outer table.
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Perpendicular striations from new bone trabeculae.
This radiographic appearance reflects a compensatory skeletal change rather than a primary bone disorder.
Pathophysiology
In thalassemia major:
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Genetic mutation causes defective hemoglobin chains (e.g., reduced or absent β-globin production).
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Ineffective erythropoiesis leads to chronic anemia.
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The bone marrow undergoes hyperplasia, expanding within the skull and facial bones.
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This expansion disrupts normal bone architecture, producing the classic “hair-on-end” radiologic appearance.
The attached case describes a patient with 94% fetal hemoglobin (HbF), a hallmark of β-thalassemia major..
Epidemiology
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Global prevalence: High in Mediterranean, Middle Eastern, and Asian populations, but also found worldwide due to migration.
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Age: Typically manifests in childhood or early adulthood if untreated.
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Genetics: Autosomal recessive inheritance pattern.
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Clinical impact: Patients often require lifelong transfusions; in the presented case, the patient had received 37 transfusions..
Clinical Presentation
Patients with severe thalassemia major often present with:
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Anemia-related symptoms: Fatigue, pallor, shortness of breath.
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Skeletal deformities: Prominent cheekbones, frontal bossing, and hair-on-end skull.
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Splenomegaly: Due to increased red blood cell destruction.
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Joint pain: As in the case of this 24-year-old man presenting with ankle and hand joint pain..
Imaging Features
The hallmark radiographic findings include:
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Figure 1. Lateral skull radiograph demonstrating generalized osteopenia in a 24-year-old male with severe thalassemia. |
Explanation: The radiograph shows diffuse bone demineralization, a common finding in patients with thalassemia major due to chronic marrow expansion and repeated transfusions.
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Figure 2. Expansion of the diploic space with vertical trabecular striations, producing the classical “hair-on-end” appearance. |
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Figure 3. Thinning of the outer table of the skull is associated with marrow expansion in thalassemia major. |
Explanation: The outer table of the skull becomes markedly thinned as the diploic space enlarges. This finding, together with vertical trabeculations, confirms the compensatory skeletal changes in severe thalassemia.
Treatment
Management of thalassemia major and associated skeletal changes includes:
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Blood transfusions: Regular transfusions to maintain hemoglobin levels and suppress bone marrow expansion.
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Iron chelation therapy: To prevent iron overload from repeated transfusions.
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Bone marrow transplantation: The only curative therapy for severe thalassemia.
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Supportive care: Pain management, folic acid supplementation, and antibiotics as needed.
Prognosis
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With treatment, Improved survival into adulthood; skeletal deformities can be minimized with early transfusion programs.
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Without treatment: Severe anemia, skeletal deformities, and early mortality.
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The presented case highlights the importance of transfusion therapy, as despite skeletal changes, the patient remains stable with ongoing care..
Questions
Question 1. What is the primary cause of the hair-on-end appearance in thalassemia?
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(A) Paget’s disease
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(B) Bone marrow hyperplasia
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(C) Hyperparathyroidism
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(D) Acromegaly
👉 Answer: (B) Bone marrow hyperplasia
💡 Explanation: Expansion of erythroid marrow in response to chronic anemia leads to diploic space widening and a hair-on-end skull.
Question 2. Which radiographic feature is most characteristic of a hair-on-end skull?
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(A) Horizontal trabeculations
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(B) Vertical striations in the skull vault
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(C) Thickened outer table
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(D) Calcified sutures
👉 Answer: (B) Vertical striations in the skull vault
💡 Explanation: The hair-on-end appearance is due to vertical trabeculae in the diploic space.
Question 3. What is the only curative treatment for thalassemia major?
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(A) Blood transfusion
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(B) Iron chelation
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(C) Bone marrow transplantation
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(D) Folic acid supplementation
👉 Answer: (C) Bone marrow transplantation
💡 Explanation: Transfusions and chelation are supportive, but hematopoietic stem cell transplantation offers a potential cure.
References
[1] D. Weatherall and J. Clegg, The Thalassemia Syndromes. Oxford, UK: Blackwell Science, 2001.
[2] A. Rund and E. Rachmilewitz, "Beta-thalassemia," N Engl J Med, vol. 353, no. 11, pp. 1135–1146, 2005.
[3] M. Cappellini, A. Cohen, E. Porter, A. Taher, and V. Viprakasit, Guidelines for the Management of Transfusion Dependent Thalassemia (TDT). Thalassemia International Federation, 2021.
[4] T. M. Aessopos, G. Farmakis, and I. Deftereos, "Skeletal changes in thalassemia," Pediatr Endocrinol Rev, vol. 2, suppl. 2, pp. 300–305, 2005.
[5] C. Musallam, A. Rivella, E. Vichinsky, and A. Taher, "Non-transfusion-dependent thalassemias," Haematologica, vol. 98, no. 6, pp. 833–844, 2013.
[6] R. G. Petrou, "Bone marrow expansion in hemoglobinopathies: radiologic evaluation," Semin Hematol, vol. 38, no. 4, pp. 299–310, 2001.
[7] J. Piga and M. Longo, "Iron chelation therapy in thalassemia," Ann N Y Acad Sci, vol. 1054, pp. 332–339, 2005.
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