Swollen, Bruised Knee in a 2-Year-Old Boy With Hemophilia A
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Acute Dx: What Cause of Sudden Illness?
The Case: A 2-year-old boy with hemophilia A (factor VIII deficiency) has had a swollen left knee for 1 day. The mother reports that she noticed a bruise on the left side of his knee 2 days earlier and that her son was limping yesterday and “keeping his left leg straight” while walking. The patient is able to bear weight and has continued his normal activities. Since the morning of presentation, he has had swelling and bruising on his left foot as well. The mother often notices bruising, especially around his diaper area. She denies any known trauma, fever, change in level of activity or appetite, and change in urination or bowel movements.
The patient sits on his mother’s lap, is calm, cooperative, and in no distress. His weight is 12.7 kg (27.9 lb). Vital signs are normal. When prompted, he walks with a limp, splinting the left knee joint. The left knee and thigh are enlarged compared with the right side. Ecchymosis is noted on the lateral aspect of the left knee, which is warm to the touch, and on the dorsal aspect of the left foot, which has mild associated swelling. The patient resists passive movement of left knee and ankle.
What do you suspect is the cause of this child’s symptoms?
•Septic arthritis.
•Knee ligamentous sprain/strain.
•Hemarthrosis/hemophilic arthropathy.
•Referred pain from the back, psoas, or hip.
(Answer and discussion begin on next page.)
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Continued
ANSWER: Hemarthrosis/hemophilic arthropathy
Discussion: Hemophilia A or B are X-linked recessive disorders that result from the deficiency of blood coagulation factor VIII or IX, respectively. Hemophilia occurs in mild, moderate, and severe forms, depending on plasma coagulation factor levels. Patients with mild hemophilia usually bleed excessively onlyafter trauma or surgery; those with severe hemophilia frequently bleed after minor trauma or without any apparent inciting event.
In patients with severe hemophilia, such as this child, bleeding into the joints is most common, followed by hemorrhage into the muscles and GI track. Bleeding into the CNS or airway can be rapidly fatal. The factors that precipitate spontaneous hemorrhage in severe hemophilia are unknown. Mucosal bleeding is uncommon in hemophilia.
Hemarthrosis is often first noted when the childbecomes ambulatoryand is uncommon in the first year of life. It is a painful and physically debilitating manifestation of hemophilia. Spontaneous hemarthrosis is so characteristic of severe hemophilia, it is almost diagnostic. Hemarthrosis typically manifests as mild discomfort and a slight limitation of jointmotion after several hours by joint swelling (Figure), cutaneous erythema, and warmth. The joints most commonly affected include the ankles, knees, elbows, and shoulders. One joint is usually affected at a time; however, multiple bleeding sites are not uncommon. The pathologicprocesses continue after the bleeding ends, and inflammation can cause further damage to the blood-filled joints.
Development of synovitis with neovascularization increases the risk of future bleeding episodes into the joint, causing a vicious circle. Eventually, changes become permanent and lead to hemophilic arthropathy—narrowing of the joint space, loss of cartilage,small bone cysts, and limitation of motion. The exact mechanisms that lead to the characteristic changes seen in synovitis are not understood fully. The number and type of hemarthroses correlate with function and future quality of life, although permanent changes can occur after only a few episodes of hemarthrosis.
Primary prophylactic treatment with factor VIII or factor IX concentrates, starting in the early years of life, can markedly reduce the risk of subsequent arthropathy. However, many patients receive treatment on demand or courses of secondary prophylaxis, not primary prophylaxis.
Patients with hemophilia and evidence or suspicion of significant bleeding require prompt factor replacement therapy; appropriate recombinant factor is usually the product of choice. Duration of treatment depends on the resolution of the hemorrhage. The half-life of recombinant factors VIII and IX is 12 hours and 24 hours, respectively. Recombinant factor VIIa may be used in patients with inhibiting antibodies toward factor VIII. On average, intravenous administration of factor VIII, 0.5 IU/kg of body weight, increases circulating factor VIII levels by about 1 IU/dL (1%). Although dosing should be individualized for each patient and for each product, higher doses of 5 to 50 IU/kg of factor VIII or 50 to 100 IU/kg of factor IX are recommended for significant hemarthrosis with hip involvement.
Clinicians should provide treatment at the earliest signs of joint bleeding. Before arthrocentesis, which is rarely necessary, 50 IU/kg of recombinant factor VIII or 100 IU/kg of recombinant factor IX should be given. Other treatment modalities, including radiation and surgical destruction of the synovium, may decrease pain and the number of bleeding episodes in patients with hemophilia; however, they do not alter the course of joint destruction.
This child was referred to the local emergency department for further evaluation. A radiograph of the left knee showed a moderate-sized effusion, which is typical for patients with hemophilic arthropathy; no fracture or other pathology was identified. A complete blood cell count showed normal white blood cells, very mild anemia, and slight thrombocytosis. The patient received intravenous recombinant factor VIII at a dose of 320 IU until he completed the total packaged dose of 1600 IU. He was observed and discharged in stable condition after 1 day.
DIFFERENTIAL DIAGNOSIS
Septic arthritis usually presents with severe pain of sudden onset; inability to bear weight; and systemic signs, such as fever or vomiting, which raise suspicion of an infectious process. The involved joint is often swollen, with associated redness and warmth. Passive range of motion usually elicits severe discomfort. Skin flora can invade the synovia as a result of antecedent cutaneous trauma, or hematogenic infection may be present. Prompt diagnosis requires joint aspiration with fluid analysis. Treatment is provided by the pediatric team in conjunction with an orthopedic surgeon.
Ligamentous sprain/strain of the knee joint may be associated with a history of trauma. Acute onset of pain along with limitation of weight bearing is expected. Certain ligaments that stabilize the knee joint (ie, the anterior cruciate) are very vascular and if torn may cause a large hemarthrosis. In cases of a sprained knee, the examination may be limited because of pain and muscle spasm with range of motion. Knee radiographs are frequently helpful. It is important to carefully assess all joints of the injured extremity and lower back to identify any other injuries. Clinicians must consider the potential for child abuse, especially in preambulatory children with certain fractures.
Referred pain to the knee is possible in both children and adults who have a primary pathologic process that involves a proximal structure, such as the ipsilateral hip joint, ileopsoas muscle, or lumbosacral spine. Thus, careful examination of the aforementioned structures is mandatory in all but the most straightforward cases of knee pain.
FOR MORE INFORMATION:
■ Hoyer LW. Hemophilia A. N Engl J Med. 1994;330:38-47.
■ Manco-Johnson MJ, Abshire TC, Shapiro AD, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med. 2007;357:535-544.
■ Manco-Johnson MJ, Riske B, Kasper CK. Advances in care of children with hemophilia. Semin Thromb Hemost. 2003;29:585-594.
■ Ross C, Goldenberg NA, Hund D, Manco-Johnson MJ. Athletic participation in severe hemophilia: bleeding and joint outcomes in children on prophylaxis. Pediatrics. 2009;124:1267-1272.