A case of osteomyelitis in a 71-year-old woman with paroxysmal nocturnal hemoglobinuria (PNH) is reported. Osteomyelitis of the jaw is a well known condition of the oral and maxillofacial region that may cause severe morbidity. It is well documented that vaso-occlusive crises in sickle cell anaemia, a hemolytic blood disorder, can make the jaw bone susceptible to osteomyelitis. The authors report a case proposing an association between PNH and osteomyelitis of the mandible.
Osteomyelitis of the jaw is a challenging condition long known to the dental and medical community. The incidence has decreased significantly over the last 50 years, most likely because of the preventive effects of modern dentistry, since osteomyelitis of the jaws is often secondary to dental infections but also because of the increased use of antibiotics. Severe forms can still be observed in maxillofacial units. The blood supply plays a critical role in the pathogenesis of osteomyelitis of the jaw and systemic vasculopathic or hematologic conditions such as sickle cell anaemia may predispose to its development . Coexisting factors influencing the pathology of the bones of the jaw provide an additional treatment challenge.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare haematological disorder with an incidence of about 1 in 1 000.000 persons/year. The disorder is caused by the expansion of hematopoietic progenitor cells that have acquired a mutation in an X-linked gene (PIGA) leading to increased sensitivity of affected red cell clones to complement mediated lysis. Common clinical signs and symptoms are paroxysmal hemolysis with hemoglobinuria and anaemia, chest pain due to esophagospasms, leukopenia and trombophilia. Median survival has been estimated as 10–15 years and thrombosis is the most frequent cause of death. Apart from bone marrow transplantation there is currently no cure. Previously, therapy was restricted to blood transfusions and anticoagulation therapy for treatment and prevention of complications. Eculizumab, a humanized monoclonal antibody that specifically binds to complement 5, has recently become available and is effective in the treatment of intravascular hemolysis and associated complications . Steroids can be used as palliative treatment for the hemolysis by decreasing complement activation.
A female, born in 1936, first noted episodes of dark urine at the beginning of the 1980s. In 1991, PNH was diagnosed and supplementation with iron and folic acid was initiated. Palliative treatment with prednisolone for the hemolysis was initiated between 1995 and 1997. Blood transfusions were given during the first 15 years after diagnosis due to clinically significant anaemia in association with hemolytic crises. Besides hematuria, signs of PNH during this period were chest pain due to esophagospasms and red skin nodules secondary to dermal vein thrombosis.
In December 1997, the first right molar in the lower jaw was extracted because of exacerbated dental infection ( Fig. 1 ). Previous to this episode, limited sclerosis surrounding the roots of the first and second right molars could be observed radiographically ( Fig. 2 ). After extraction of the tooth, the patient experienced recurrent episodes of pain from the right mandible and, in September 1998, the second right molar was extracted due to recurrent pain and increased mobility. After this extraction, complete clinical healing of the socket and the mucosa required one year. During and after this period, the patient reported bursts of pain and radiography demonstrated increasing sclerosis ( Fig. 3 ). Superficial surgical debridement of the right mandible was performed in 1999, without mitigating the pain. A diagnosis of chronic osteomyelitis of the jaw was assigned on the basis of the clinicopathologic features and radiographic evidence. Long-term treatment was given with various regimes of painkillers such as ibuprofen 600 mg three times daily (t.i.d.), paracetamol 1 g four times daily (q.i.d.), diclofenac 50 mg t.i.d. and celecoxib 100 mg twice daily (b.i.d.). Over the years, several and repeated courses of various antibiotics were given, mostly orally (PO) but also intravenously (IV) with drugs and regimes such as imipenem IV 1 g q.i.d. for 14 days, ciprofloxacin PO 500 mg b.i.d. for 7 days, mecillinam PO 200 mg b.i.d. for 7 days, ceftazidime IV 1.5 g t.i.d. several courses for 3–7 days, amoxicillin PO 500 mg t.i.d. for 7 days, phenoxymethylpenicillin PO 2 g b.i.d. for 10 days and metronidazole PO 400 mg t.i.d. for 7 days. Most of them were primarily given for urinary tract and lower airway infections and had no impact on the osteomyelitis.
By this time, the patient, the physicians involved in the treatment of the PNH and the oral and maxillofacial surgeon treating the osteomyelitis had noticed a chronological association between the episodes of hemolytic crises and the bursts of pain from the jaw. With few exceptions, the pain appeared within a couple of days of the start of a hemolytic crisis. The patient also experienced exacerbations of the pain during the night. The only treatment effective in reducing the symptoms from the osteomyelitis of the jaw was predisolone, used for reducing the hemolysis. The patient had used the drug since the mid-1990s with a standing dose of 5–10 mg/day which was increased to 30–40 mg/day when the hemolysis occurred.
In 2000, MRI was performed with contrast enhancement ( Fig. 4 ). It showed a generalized sclerosis from the canine to the ramus of the right mandible without signs of oedema. An increased thickness of the mandible and cortical bone was noticed but it was concluded that there was no ongoing inflammatory activity.