Introduction
Sickle cell disease (SCD)1 includes a group of related genetic diseases affecting hemoglobin structure,2 and is considered the most common genetic blood disorder among children.3 SCD frequently occurs in individuals whose ethnic origin is Africa,4 Middle East,5 Asia,6 Southern Europe,7 Central or South America,8 or the Caribbean.9 Sudan includes mosaic ethnic diversity that ranges from Afro-Arab and Arab to African tribal.4 This ethnic diversity includes groups with Negroid genetic features, with a recognized history in areas such as Nilotes and Nuba.10
Acute skull soft syndrome is an uncommon complication of sickle cell anemia.11 The pathogenesis and mechanism underlying the complication of acute skull soft syndrome is not fully understood. In addition, no information has been gained from the previous studies of acute skull soft syndrome for suffers in Sudan. The case of such presented herein is thus novel and of particular importance to Sudanese clinicians,12 and we hope it will serve to increase knowledge and kindle awareness of this complication in Sudan.
Case Report
A 20-year old male with a known history of sickle cell anemia, diagnosed at the age of 2 years-old, came to our clinic at Almawada (a private hospital) on May 18, 2019. The patient complained of headache and generalized joint pain that had begun 1 day prior to clinic presentation. The patient described the headache as constant, with mild frontal pain and not preceded by an aura nor associated or aggravated by anything, and partially relieved by paracetamol tablets. He denied any visual changes, vomiting, altered level of consciousness, neck pain, or variation of headache with positional changes or during the hours of the day. He also reported isolated joint pain involving wrists, knees and hips. The pain had severity score of 6/10 (according to self-judgment) and was dull in quality but not interfering with movement. There was moderate grade fever and the pain had intermittent association with nausea, but no shivering or rigger. The patient also reported a burning sensation during micturition. There were no complaints involving any other organ systems.
The patient had a history of multiple previous hospital admissions, due to sickle cell crises. He had no history of diabetes mellitus, hypertension or any similar conditions, but he had been diagnosed 1 month previous with gallstone (“not operated”). The patient was on regular folic acid tablets, 5 mg daily, and not known to be allergic to any type of medication. On examination, the patient looked ill and in pain, and was pale and jaundiced. Vital signs were all within normal parameters, except for the body temperature at 38 °C. Blood pressure was 120/80 and heart rate was 70 beats/m. The patient was fully conscious and oriented when the central nervous system tests were performed. The Mini-Mental State Examination (commonly referred to as the ‘MMSE’) score was 30/30. All cranial nerves were intact, and Kernig’s and Brudzinski’s signs were negative.
Upper limbs showed no muscle wasting or fasciculations, and there was intact normal tone sensation; power was grade 5, and deep tendon reflex was +2 bilaterally. The lower limbs showed no muscle wasting or fasciculations, normal tone and intact sensation; power grade was 5, deep tendon reflex was +2 bilaterally, and gait was normal. Musculoskeletal examination of hands showed no swelling, tenderness, deformities, muscle wasting, skin rash or signs of dactylitis, and normal temperature and intact radial pulses. Phalen’s test was negative, with both knees and hips showing not swelling nor hotness but tenderness was present; the range of movement was normal. The cardiovascular examination also showed normal first and second heart sounds, with no murmurs or signs of heart failure. Clear breath sounds were heard bilaterally in chest examination. Results from blood sample testing for complete blood count, renal function and blood glucose are summarized in Table 1.
Table 1Lab investigations and findings for the patient
| Date | Investigation | Result | Reference value |
|---|
| 18/5/2019 | Blood urea nitrogen
Serum creatinine
Serum Na+
Serum K+
Random blood glucose
Immunochromatographic (ICT) for malaria | 141 mg/dL
18.5 mg/dL
139 nm/L
3.6 nm/L
141 mg/dL
Negative | 10–50 mg/dL
0.7–1.4 mg/dL
131–149 nm/L
3.1–5 nm/L
79–140mg/dL |
| 20/5/2019 | Serum Na+
Serum K+ | 137 nm/L
3.6 nm/L | 131–149 nm/L
3.1–5 nm/L |
| 21/5/2019 | White blood cells
Red blood cells
Blood hemoglobin
Mean corpuscular volume
Platelets
Blood urea nitrogen
Creatinine | 12.7 cells/cumm
2.01 mill cells/cumm
6.5 g/dL
98 fl
98,000 cells/cumm
25 mg/dL
1.5 mg/dL | 4–10 cells/cumm
3.8–5 mill cells/cumm
12.5–15.5 g/dL
78–98 fl
150,000–450,000 cells/cumm
15–45 mg/dL
0.7–1.4 mg/dL |
Upon admission, the patient was immediately begun on intravenous normal saline (1 L/8 hours) with ciprofloxacin infusion (200 mg intravenously every 12 hours), tramadol tablets (once per day), paracetamol infusion (1 g/ 6 hours), and 4 U of packed red blood cells. On the third day of admission, the headache reached its maximum, being associated with scalp swelling and tenderness (Fig. 1). There was no loss of consciousness, visual change, projectile vomiting or neck stiffness. The patient denied history of head trauma, and stated he had never experienced such symptoms before. Again, the patient was negative for Kernig’s and Brudzinski’s signs. Brain magnetic resonance imaging (MRI) was conducted and revealed no abnormalities (Fig. 2). The diagnosis was made clear as soft skull syndrome. The patient was treated with conservative management of intravenous normal saline (1 L/8 hours) and pethidine injection (50 mg twice every day). After two days, the patient fully recovered and was discharged.
Discussion
SCD is considered to be one of the most common causes of chronic anemia among pediatric patients of African descent.13 Chronic anemia, as in our case, leads to an increase in the demands of blood production and development of an extramedullary or intramedullary hematopoiesis.14 As such, chronic anemia is linked with elevated cardiac output and increased blood flow velocity, resulting in arterial tortuosity in many cases.15,16
Acute soft skull syndrome is a rare manifestation of SCD, and the pathogenesis is not clearly understood, although it is believed to be related to infraction of the skull due to expansion of intramedullary hematopoietic tissues leading to disruption of the outer and inner skull margins and in turn resulting in softening of cortical bones.17 The differential diagnosis of a patient with acute soft head syndrome must include other causes of hematoma, such as trauma (which our patient had no history of), bleeding diathesis (in the present case, the platelet count and bleeding profile were within the normal range), and intracranial pressure (we excluded by the absence of any related features, such as altered level of consciousness, vomiting or visual changes). Clinical examination will also exclude any relative causes of skull swelling, such as lymph node enlargement due to any reason.
MRI and computed tomography (CT) scans of the skull have an important role in the differential diagnosis of sicker patients with acute soft swelling, as they are both able to detect bone infarction.18 MRI, However, is more sensitive than CT in detection of bone infraction.18 The presented patient underwent MRI and showed diploic space marrow signal changes consistent with known disease, which overall indicated an unremarkable finding. A contract-enhanced MRI will demonstrate an area of heterogeneous and rim-like enhancement,18 and T2-weighted and short-inversion time inversion recovery MRI can detect areas of the high-intensity bone marrow infarction and edema.18 Although, neither one of those investigations could afforded by our patient.
Acute soft head syndrome due to sickle cell anemia is well known to be resolved by the same treatment of other sickle cell crises, that being conservative management (intravenous fluids and analgesics).18 Our patient did very well after receiving the intravenous fluids and tramadol.
In conclusion, this complication of SCD is uncommon but other reported cases along with ours serve to emphasize the need and desire for recognizing skull infarction, perhaps resulting in sub-periosteal hematomas as causes of skull swellings and headache in sickle cell patients.
Abbreviations
- CT:
computed tomography
- MRI:
magnetic resonance imaging
- SCD:
sickle cell disease
Declarations
Patient consent
Consent was obtained from the patient.
Ethical approval
Ethical approval was obtained from Sudan Federal Ministry of health.
Funding
No funds or financial aid were received for this study.
Conflict of interest
All authors declare there are no conflicts of interest.
Authors’ contributions
Case diagnosed and treatment supervision (ZIT), follow up (SEA, WME, SMEO), drafting of the manuscript (MEAE), analysis and interpretation (MMAH, HOA), critical revision of the manuscript for important intellectual content (MDY), study supervision (AAA).