Scalp Swelling and Headache in a 12-year-old Boy

Abstract

A 12-year-old boy with sickle cell disease (SCD) is admitted to a hospital in Mwanza, Tanzania, with acute onset of periorbital and scalp swelling. Associated symptoms include fever, headache, difficulty breathing, and back pain. Because resources in sub-Saharan Africa are limited, access to comprehensive care for patients with SCD is variable. The general principles of management focus on early diagnosis, parental education, prevention of infection with vaccinations and prophylactic medications, prompt treatment of infection and pain, the use of hydroxyurea for stroke prevention, and blood transfusions for life-threatening anemia. This patient has a known diagnosis of SCD but has infrequent pain episodes and no previous transfusions. He is not receiving hydroxyurea or prophylaxis against bacterial infections or malaria. He has no history of stroke and no known head trauma.On presentation he is afebrile and his heart rate is 120 beats/min, respiratory rate is 40 breaths/min, and blood pressure is 105/75 mm Hg. His oxygen saturation is 92% in room air. Physical examination is significant for pallor, periorbital edema, scalp edema, dyspnea without adventitious lung sounds, and splenomegaly with diffuse abdominal tenderness. His scalp edema is fluctuant and extends posteriorly from the periorbital region, encompassing the entire scalp. Swelling is most prominent in the frontal and parietal areas. The overlying skin is nonerythematous and nontender but is warm to the touch. His neurologic examination has no focal findings, although generally he appears tired. Initial laboratory results demonstrate a white blood cell count of 84,000/μL (84×109/L) with a lymphocytic predominance (57%), a hemoglobin level of 3.1 g/dL (31 g/L), and a platelet count of 121×103/μL (121×109/L). The patient’s baseline blood cell counts are not known. Malaria smear is negative. Blood culture is sent. Further laboratory evaluation is limited at this time due to financial and resource constraints.The patient’s clinical picture raises concern for many commonly seen complications of SCD, including a vaso-occlusive pain crisis of his back, acute chest syndrome (ACS), splenic sequestration, and stroke. Due to the limited availability of opioids at his hospital, he is given diclofenac for analgesia to treat his presumed vaso-occlusive pain crisis. He is also started on intravenous fluids. A diagnosis of ACS typically requires both pulmonary symptoms and evidence of a new pulmonary infiltrate on chest radiography. Radiography is not readily available in many medical centers in sub-Saharan Africa, and thus physicians must rely on their clinical judgment to diagnose ACS. This patient is not able to have chest radiography performed, but given his fever, tachypnea, and hypoxemia, he is diagnosed clinically as having ACS and is treated empirically with azithromycin and ceftriaxone. Headache and lethargy raise concern for stroke, but access to a computed tomographic (CT) scanner is delayed until the family can provide payment for the cost of imaging. The patient is transfused 1 U of whole blood given the severity of anemia and the presence of acute complications of SCD. Posttransfusion hemoglobin level is not measured.Within 2 days of hospitalization his respiratory symptoms and pain improve but he continues to have periorbital and scalp swelling with fevers. Antibiotic coverage is broadened to piperacillin-tazobactam and metronidazole. A CT scan of the head without contrast and a review of the literature reveal a rare complication of SCD.The head CT performed shows a subgaleal hematoma over the frontal and bilateral parietal bones without intracranial pathology such as stroke or epidural hematomas. A spontaneous subgaleal hematoma is an unusual complication of SCD but should be in the differential diagnosis of a child with SCD presenting with scalp swelling.SCD refers to a group of inherited red blood cell (RBC) disorders in which a point mutation in the β-globin chain results in abnormal hemoglobin (HbS) that can lead to sickling of RBCs. The sickled RBCs adhere to and damage endothelial layers of blood vessels; the subsequent vaso-occlusion can then cause pain, ACS, priapism, stroke, and/or splenic sequestration. Patients with SCD also develop chronic anemia due to hemolysis of sickled cells; this anemia can be exacerbated during an acute vaso-occlusive episode. Patients with SCD can have variable phenotypic expression due to variations in genotypes that lead to the disease. Some patients with SCD inherit 2 abnormal copies of the gene that controls hemoglobin β-globin chain expression; these patients are referred to as having homozygous sickle cell anemia (HbSS). In other patients, the gene for HbS can be coinherited with other hemoglobinopathies (such as a copy of HbC, HbD, or β-thalassemia), resulting in a variety of clinical syndromes.The clinical manifestations of SCD are most severe in patients with HbSS or HbSβ0-thalassemia. Patients with HbSβ0-thalassemia have a clinical severity similar to those with HbSS; in both genotypes, there is a complete absence of normal β-globin chains, resulting in the absence of normal HbA. In these patients, most hemoglobin is present in the form of abnormal HbS. Patients with HbSβ+-thalassemia still have HbA, but in a reduced amount, and, therefore, have a more benign clinical course. Patients with HbSC disease also typically have a milder degree of anemia and less frequent, although similar, complications compared with individuals with HbSS.Spleen-related complications of SCD also vary by genotype. For all patients with SCD, chronic vaso-occlusion affects the spleen’s size and function. During the first few months to decades of life, silent occlusive episodes result in functional hyposplenism and, eventually, functional asplenia. Patients are at increased risk for infection with encapsulated bacteria, which the poorly functioning spleen can no longer remove from the bloodstream. Most children with HbSS have evidence of impaired spleen function by 12 months of age. (1) Patients with HbSC or HbSβ+-thalassemia may have less frequent sickling than patients with HbSS and so may not develop functional asplenia until later in childhood or early adulthood. (1) In these patients, thus, the risk of infection with encapsulated bacteria may not be present until later in life. In addition, the fibrosis and scarring due to chronic vaso-occlusion also causes the spleen to atrophy and shrink over time. Most children with HbSS have evidence of complete atrophy of the spleen by age 5 years. (1) Our patient had splenomegaly; in other words, his spleen had not yet atrophied. Given that our patient has reached the second decade of life without a life-threatening infection, need for blood transfusions, frequent vaso-occlusive episodes, or splenic atrophy, it is likely that he has a heterozygous sickle cell disorder such as HbSC or HbSβ+-thalassemia.According to the World Health Organization (WHO), more than 300,000 infants worldwide are born with SCD each year, with the greatest burden in sub-Saharan Africa. (2) Tanzania, where our patient lives, has the fourth highest birth prevalence of SCD in the world. (2) In resource-rich countries, neonates can be identified via newborn screening programs and can access care promptly, resulting in lower rates of complications and early death. However, most patients with SCD are from low-resource countries and do not receive the same screening or management. Many children die of pneumococcal sepsis, splenic sequestration, or severe malaria before a diagnosis of SCD is even made. (3) According to the WHO, SCD contributes to 6.4% of deaths in African children younger than 5 years. (2)There is currently no national newborn screening program in Tanzania for SCD. Most children are diagnosed via a sickling test after they present with 1 or more complications that raise concern for SCD. A sickling test is the primary method of diagnosis and detects the inappropriate sickling of RBCs after a patient’s blood is mixed with a chemical that reduces the oxygen tension in the blood. This test is unreliable in infancy, however, given the high concentration of fetal hemoglobin and can lead to false-negatives. (4) It also cannot distinguish between HbSS and heterozygous genotypes. Ideally, after a presumptive diagnosis via a sickling test, a patient’s genotype would be identified via hemoglobin electrophoresis or high-performance liquid chromatography, but these are not available in many of the medical centers in Tanzania and may be cost-prohibitive for patients. This may be why our patient was known to have SCD but the genotype was unknown.A subgaleal hematoma forms when there is bleeding in the potential space between the periosteum and the scalp aponeurosis. The space crosses suture lines and extends from the orbital regions anteriorly to the ears laterally and the neck posteriorly; hemorrhages into this space can cause significant blood loss and be life-threatening. Pediatricians may be more familiar with diagnosing and managing subgaleal hematomas in the newborn period because trauma from delivery can cause rupture of emissary veins and bleeding into this potential space. Nontraumatic subgaleal hematomas, as seen in this patient, are rarely described in the literature. (5)(6)(7)(8)(9)(10)(11)(12) In a review of the SCD literature, we found 3 case reports of isolated subgaleal hematomas (6)(7)(8) and 5 of patients with both subgaleal and epidural hematomas. (5)(9)(10)(11)(12) In case reports focusing on epidural hematomas in SCD, associated scalp swelling was described in approximately half of the patients. (11)(12) In most patients with subgaleal hematomas, the presenting features were headache and scalp swelling.The pathophysiology of subgaleal hematoma formation in SCD is not as well understood, and there may not be a single uniform explanation for all cases. Patients typically have a preceding or current vaso-occlusive crisis at the time of the scalp swelling. Most cases are attributed to bone infarction, which disrupts the skull margins and causes periosteal elevation with extravasation of blood into the subgaleal, and often epidural, spaces. (10) It has also been suggested that the increased hematopoiesis in response to acute anemia disrupts the skull margins and results in the spontaneous extravasation of blood. (5)(10) Other theories propose that insufficient venous drainage from skull infarction precipitates edema and hemorrhage, (5) or that spontaneous rupture of blood vessels near the infarcted bone leads to bleeding. (7)This patient’s presentation is concerning for multiple complications of SCD that require emergency evaluation and treatment. It is important for patients, families, and providers to know the patient’s “baseline” hemoglobin value to guide management when an acute complication arises. For people with HbSS disease, the baseline hemoglobin level is typically 6 to 8 g/dL (60–80 g/L); acute anemia is defined as a decrease from the baseline by 2 g/dL (20 g/L) or more. (13) If a provider suspects acute anemia, then a patient’s blood should also be typed and screened for antibodies at the time of presentation to avoid a delay in transfusion. A reticulocyte count can help determine the cause of anemia (ie, decreased RBC production, increased hemolysis, or sequestration).Although this patient’s baseline hemoglobin level is not known, and a reticulocyte count could not be performed, one can deduce from his physical examination findings (tachycardia, tachypnea, and splenomegaly) that splenic sequestration and ACS could be contributing to his anemia. Evaluation for ACS should include a chest radiograph and measurement of oxygen saturation. Obtaining a blood culture and starting empirical antibiotics in the setting of a fever (>101.3°F [>38.5°C]) is crucial because most patients are at increased risk for bacterial infection. Empirical antibiotics in this setting typically include an intravenous cephalosporin and an oral macrolide. Any patient with SCD presenting with a severe headache, altered mental status, seizures, or other neurologic signs or symptoms should be evaluated for acute stroke with neurologic imaging. Usually, head CT is the quickest mode of imaging to look for hemorrhage or ischemia. It would also be important to get a coagulation profile (international normalized ratio, activated partial thromboplastin time, prothrombin time) given the potential for coagulopathy.Donor RBC transfusions containing normal hemoglobin can be administered to patients with SCD in the form of a simple blood transfusion (10 mL/kg) or exchange transfusion to reduce the percentage of circulating RBCs with abnormal hemoglobin. Transfusions can be used in the treatment and prevention of many SCD complications but are not beneficial in every clinical scenario. Common potential indications for transfusion are present in this patient, including stroke, symptomatic ACS combined with a decreased hemoglobin level of 1 g/dL (10 g/L) below baseline, and acute splenic sequestration with severe anemia. (13) In addition, should surgical procedures under general anesthesia be anticipated, National Health, Lung, and Blood Institute recommendations include prophylactic transfusions in some clinical scenarios to target a preoperative hemoglobin level of at least 10 g/dL (≥100 g/L) to avoid postoperative sickle cell–related complications. (13) It is also important to transfuse slowly if there is concern for chronic anemia to avoid the theoretical risk of transfusion-associated circulatory overload. The decision to transfuse should be made in consultation with a sickle cell expert given the intricacies of the risk-benefit assessment. (13)Subgaleal hematomas in patients with SCD are described in the literature only through case reports, so there are no standard guidelines for management. These patients should be evaluated with brain imaging, if available, because many of the causes of subgaleal hematomas can also lead to intracranial bleeding. (5)(10)(11) If head imaging reveals intracranial hemorrhage, then neurosurgical intervention may be warranted to prevent or treat associated midline shift or herniation. However, most cases of isolated spontaneous subgaleal hematomas without intracranial hemorrhages resolve with conservative treatment of the concurrent vaso-occlusive crisis using analgesics, intravenous fluids, and blood transfusions. (6)(7) In previous case reports, empirical antibiotics were used given the difficulty in distinguishing infarction from osteomyelitis. (6)(7)(9) Most patients with isolated subgaleal hematomas will make a full recovery.In the context of the patient’s swelling, the medical team felt that the CT findings were consistent with a subgaleal hematoma. This patient had persistent fevers and significant leukocytosis on admission, so infection could not be excluded. Given that a hematoma is an ideal medium for bacterial growth, there was concern that the hematoma had become infected, an abscess had formed, or there was underlying osteomyelitis. The patient went to the operating room to have the fluid evacuated and cultured to see whether a pathogen could be isolated. Grossly, only blood was drained without overt signs of superinfection. Drains were left in place to prevent repeated accumulation of blood and were removed after 3 days. Peripheral blood and hematoma aspirate cultures remained negative. Due to persistent fevers, he was switched to amikacin therapy. Fevers resolved in the subsequent 72 hours, and the remainder of the subgaleal hematoma gradually resolved without further intervention. He was discharged from the hospital, making a full recovery, after completing a several-week course of intravenous antibiotic therapy for a presumed bacterial superinfection.