Periodontal considerations in a patient with glucose-6-phosphate dehydrogenase deficiency with associated pancytopenia: A rare case report

Abstract

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme defect in humans. G6PD deficiency is widely distributed in tropical and subtropical parts of the world and a conservative estimate is that at least 500 million people have a G6PD deficient gene. In several of these areas, the frequency of a G6PD deficiency gene may be as high as 20% or more. The vast majority of people with G6PD deficiency remain clinically asymptomatic throughout their lifetime. However, all of them have an increased risk of developing neonatal jaundice and a risk of developing acute hemolytic anemia when challenged by a number of oxidative agents. The most important treatment measure is prevention: Avoidance of the drugs and foods that cause hemolysis.

INTRODUCTION

Glucose-6-phosphate dehydrogenase (G6PD or G6PDH) deficiency was first identified by Dr. Ernest Beutler in 1953.[1] It is an X-linked recessive hereditary disease characterized by abnormally low levels of G6PD, a metabolic enzyme involved in the pentose phosphate pathway, especially important in red blood cell metabolism.[2]

G6PD deficiency is a prime example of a hemolytic anemia (HA) due to interaction between an intracorpuscular and an extracorpuscular cause, because in the majority of cases hemolysis is triggered by an exogenous agent. Thus, the acute HA of G6PD deficiency is largely preventable by avoiding exposure to triggering factors of previously screened subjects.[3]

G6PD deficiency is the most common human enzyme defect,[2] yet, there has been no reported case of G6PD deficiency associated with pancytopenia and bone loss.

CASE REPORT

A 34-year-old female patient prediagnosed with G6PD deficiency complaining of gingival swelling and bleeding since 9 years and progressive spacing between maxillary and mandibular anterior teeth reported to the outpatient department of Periodontology of the college.

History dates back to the year 2002 when the patient developed some bleeding complications during her pregnancy and was admitted in the hospital. During her stay in the hospital, the patient showed signs of petechiae and ecchymosis on the extremities. The patient also developed oral symptoms like gingival bleeding and palatal ecchymosis. It was then that she was diagnosed with Aplastic anemia/pancytopenia with hypocellular bone marrow and G6PD deficiency. She was also referred to their dental department for consultation regarding her oral condition. Hospitalization further deteriorated her oral hygiene, thus complicating her already compromised oral condition. Her platelet count kept decreasing and at the time of delivery her platelet count was 5000 only. The newborn boy was also diagnosed with G6PD deficiency but was asymptomatic.

The patient was then hospitalized for another 6 months after delivery during which her physical condition and her platelet count improved. Since then the patient experienced gingival swelling and bleeding and progressive spacing between her upper and lower anterior teeth. She visited several general dentists but because of her underlying medical problem she was refused treatment by some while some provided her oral prophylaxis on her written consent. She developed some improvement in the oral condition but finally she was referred to the department of Periodontology of the college for expert opinion.

Intra-oral examination showed signs of gingival inflammation, the changes being more pronounced in the maxillary and mandibular anterior region. The gingiva was dark pink, edematous, and enlarged with rolled and rounded margins with less pronounced scalloping. There was loss of stippling and the gingiva was smooth and shiny. Also, gingival recession and clefting was present on the palatal aspects of maxillary anterior teeth [Figures 1 and 2]. There was pus exudation on palpation. Pathological migration was also evident in the same region.

Figure 1.

Preoperative photograph showing papillary swelling and inflammation

Figure 2.

Preoperative palatal view of maxillary arch showing clefting and inflammation of marginal gingiva and petechiae on palatal surface

Radiographically, generalized bone loss was evident which was more pronounced in the maxillary and mandibular anterior region [Figure 3].

Figure 3.

Preoperative OPG showing bone loss mainly in upper and lower anterior teeth

Clinically, deep periodontal pockets were present in the maxillary and mandibular anterior teeth on probing using a periodontal probe with Willams markings.

DISCUSSION

G6PD deficiency, resulting from mutations in the G6PD gene, is well known in humans as a common cause of pathology, specifically of HA.[4] All mutations that cause G6PD deficiency are found on the long arm of the X chromosome, on band Xq28.[5] In many of these mutants, G6PD deficiency is not extreme and the clinical manifestations are limited, as they occur only when an exogenous agent triggers hemolysis.[4] The clinical picture can develop upon ingestion of fava beans (favism), during the course of infection, or after exposure to certain oxidative agents.[5]

G6PD-deficient red blood cells (RBCs) are more susceptible to oxidative stress and have a shorter lifespan.[5] Acute HA can be caused by infections, drugs, and nutrients. If a considerable proportion of hemolysis takes place in the spleen, as is often the case, splenomegaly may become a prominent feature and hypersplenism may develop, with consequent neutropenia and/or thrombocytopenia resulting in pancytopenia. Aplastic anemia or pancytopenia has also been found to be associated with pregnancy.[3]

Pancytopenia affects oral conditions adversely. Oral changes include pale discoloration of the oral mucosa, increased susceptibility to infections, and bleeding spontaneously or on slightest provocation. Gingival tissues represent an abnormal response to local irritation, the severity of which is dramatically alleviated by the removal of local irritant.[6]

Studies have shown that accumulation of microbial biofilm, dental plaque, on tooth surfaces results in the development of an inflammatory process around gingival and periodontal tissues leading to their breakdown.[7] Hospitalization affects the maintenance of oral hygiene in patients both physiologically and psychologically.

Also, increase in number of certain anaerobic bacteria in subgingival plaque due to hormonal changes occurs in pregnancy. Moreover, maternal immune system is suppressed during pregnancy.[6]

Thus, pregnancy and pancytopenia followed by hospitalization deteriorated the oral tissues of the patient. Lack of proper dental treatment by the general dentists due to the patient's underlying medical condition for about 9 years further exacerbated the oral problem of the patient to the present status.

The treatment in the present scenario included proper oral prophylaxis, soft tissue debridement and surgical therapy after consultation and clearance from the hematologist and written consent from the patient. Special care was taken regarding her current blood profile including all the relevant blood tests and individual cell counts, which were discussed in detail with her hematologist. All the drugs that are contraindicated in G6PD-deficient patients were avoided [Table 1] and only those drugs which are safe in G6PD-deficient patients were given [Table 2].

Table 1.

Drugs and Chemicals that should be avoided by persons with G6PD deficiency

Table 2.

Some common drugs that can be safely administered in therapeutic doses to Glucose-6-phosphate dehydrogenase-deficient subjects without nonspherocytic hemolytic anemia

The surgical therapy included open flap debridement and regenerative periodontal therapy wherever required and possible.

The postoperative presentation included resolution of the patient's symptoms of gingival bleeding and swelling. The clinical presentation shows reduction in the signs of gingival swelling, with reduction in size of tissues, reduction in probing depths and a significant gain in clinical attachment levels. There was no bleeding on probing and the signs of gingival inflammation were also resolved [Figures 4–6].

Figure 4.

Postoperative photograph showing resolution of gingival inflammation

Figure 6.

Postoperative left side

Figure 5.

Postoperative right side