Cancrum oris

Cancrum oris also known as Noma or gangrenous stomatitis is a severe, preventable and often fatal rapidly progressing infection of the mouth and face that requires urgent and intensive medical and surgical care ¹, ², ³, ⁴, ⁵, ⁶, ⁷. The term noma originates from the Greek word “nomein” which means “to devour” or “to graze” ⁸, ⁶. Cancrum oris or noma usually begins as an ulcer on gums (the tissues that support your teeth) and rapidly spreads into the jawbone, cheek, and soft tissues of the face. This is followed by death of the facial tissues and fatal sepsis. Cancrum oris or Noma is associated with a reported 90% mortality rate within weeks after onset, if left untreated ². Survivors are left with severe facial disfigurement and impairments in breathing, swallowing, speaking and vision ¹, ², ⁵, ⁷.

The exact cause is cancrum oris or noma is still poorly understood, but noma may be due to a certain kind of bacteria ¹, ². Previous observational studies have suggested that risk factors for development of cancrum oris or noma include severe malnutrition, low birthweight, absence of breastfeeding, poor oral hygiene, co-morbidities, proximity of livestock to area of residence, large family size, access to unsafe drinking water and living in a village with a high prevalence of acute necrotizing gingivitis ⁹, ¹⁰, ¹¹, ¹². Recently, an increased incidence of cancrum oris or noma has been reported in higher resource settings in patients with immunosuppressive diseases such as human immunodeficiency virus (HIV) ¹³, ¹⁴, ¹⁵, ¹⁶, ¹⁷.

Cancrum oris or noma mostly affects children aged 2 to 6 years old living in poor communities who lack access to basic nutrition, hygiene services, and health care, although cases are reported in immunocompromised adults ¹, ². One theory for the higher incidence of noma in children aged two to six years, is that this is the teething age when deciduous teeth are formed ¹⁸. This formation slows down the circulatory flow to the gums due to compression, leaving the oral cavity more susceptible to infections ¹⁸. A Zambian study theorized that during the weaning period from breastfeeding, children eat more solid food, which was less nutritious and less sterile than breast milk, and this placed them at potential risk for noma development ¹⁹. Another study showed that if weaning foods are prepared under unhygienic conditions, they are frequently contaminated with pathogens and are a major factor in the cause of diarrheal diseases ²⁰, a further reported risk factor for noma ²¹.

In recent years, noma has been reported in many countries around the world, but primarily in low and middle income countries in Africa and Asia ³. Epidemiological data on cancrum oris or noma are scarce, but a current estimate of the global incidence is 30,000 to 40,000 cases per year, with a mortality rate of approximately 85% and a burden of disease calculated to be a loss of 1–10 million disability-adjusted life years ⁷.

Cancrum oris or noma is diagnosed using World Health Organization (WHO) clinical criteria that differ according to the different stages of disease progression. There is currently no point of care diagnostic test. The World Health Organization (WHO) classifies cancrum oris or Noma into 5 clinical stages ¹, ²:

• Stage 0 – Gum inflammation (simple gingivitis);
• Stage 1 – Acute necrotizing gingivitis;
• Stage 2 – Edema;
• Stage 3 – Gangrene;
• Stage 4 – Scarring;
• Stage 5 – Complications.

The first 4 stages (Stage 0 to 4) are the acute stages of noma lasting only a few weeks. Deaths in noma patients are primarily reported to be due to starvation, aspiration pneumonia, respiratory insufficiency or sepsis ²², ²³, ⁷.

Early detection is essential, as therapy is most effective at the early reversible stages of noma when it appears as aggressively swollen gums (acute necrotizing gingivitis). Commonly available broad-spectrum antibiotics with proper nutrition together with practices to improve oral hygiene, disinfectant mouthwash (salt water or chlorhexidine could be used) helps stop the disease from getting worse ¹, ². Once cancrum oris or noma progresses past early reversible stages (Stage 0 to 4), the complications of noma are numerous and include difficulty in eating, drinking, seeing and breathing ¹, ², ²⁴, ²⁵. Plastic surgery may be necessary to remove destroyed tissues and reconstruct facial bones. This will improve facial appearance and the function of the mouth and jaw ²⁶. For those who seek care for these complications, it can mean hospital stays of many months with multistage surgical treatments that can take years to complete. Survivors often need complex surgical reconstruction to restore form and function ²⁶. Trismus (a restriction in mouth opening) is one of the most disabling complication ²⁷, ²⁸ and can lead to complications such as aspiration, malnutrition, poor oral hygiene, speech deficits, a compromised airway, and pain ²⁹.

Cancrum oris causes

The exact cause is cancrum oris or noma is still poorly understood, but noma may be due to a certain kind of bacteria ¹, ², ³⁰, ⁷. Previous observational studies have suggested that risk factors for development of cancrum oris or noma include severe malnutrition, low birthweight, absence of breastfeeding, poor oral hygiene, co-morbidities, proximity of livestock to area of residence, large family size, access to unsafe drinking water and living in a village with a high prevalence of acute necrotizing gingivitis ⁹, ¹⁰, ¹¹, ¹². Even though noma primarily affects young children ²⁴, noma cases in adults, mostly in conjunction with other severe infections like human immunodeficiency virus (HIV), cancer or oral myiasis have been reported ³¹, ³², ³³, ³⁴. Recently, an increased incidence of cancrum oris or noma has been reported in higher resource settings in patients with immunosuppressive diseases such as human immunodeficiency virus (HIV) ¹³, ¹⁴, ¹⁵, ¹⁶, ¹⁷.

A range of organisms have been identified in the oral flora of noma patients, but none have been consistently present, casting doubt on a specific organism’s role in the development of noma ³⁵, ³⁶, ³⁷, ³⁸, ³⁹, ⁴⁰, ⁴¹. Other studies have noted that the characteristics of noma are similar to that of an opportunistic infection, implicating a change in the equilibrium of commensal bacteria due to a derailment of host defences ⁴², ⁴³, ³⁹, ⁴⁴. Evidence that supports noma being an opportunistic infection rests in the fact that most cases have concurrent infections or occur in immunocompromised individuals ⁴², ¹⁹, ³⁶, ¹⁸, ⁴⁵, ⁴⁶, ⁴⁷, ⁴⁸.

It has been speculated that Borrelia vincentii and Fusobacterium are prominent bacteria in noma lesions ⁴⁹, ⁵⁰. Symbiotic relationships between fusiform bacilli and non-hemolytic streptococci and staphylococci have been considered significant factors in the development of noma ⁵¹. Recent reports suggest that besides fusiform bacilli and spirochetes, other anaerobic bacteria are present in a relatively high proportion of noma lesions ⁵⁰. Fusobacterium necrophorum is considered a key component; this organism produces dermatotoxins, which could explain the rapid progression of the disease ⁵². Fusobacterium necrophorum is acquired by impoverished children through fecal contamination of water, which occurs when residential facilities are shared with animals and sanitation is very poor ⁸. Prevotella intermedia has the ability to break down lipid structures, which contributes to tissue destruction ⁸. It also produces proteolytic enzymes
capable of breaking down immunoglobulin G (IgG), which impedes elimination of microorganisms ⁵¹. Some reports have suggested that these microorganisms are resistant to penicillin ⁵⁰, which emphasizes the need for culture and sensitivity tests before administration of antibiotics.

Recent studies using genomic approaches showed an imbalance in the normal oral flora with acute noma seems to be characterized by the diminution of Capnocytophaga and Fusobacteria genera and by the increase of Prevotella genus ⁵³, ⁵⁴, ⁵⁵. Prevotella intermedia was already reported in previous studies undertaken with classical cultures ⁴⁹. Prevotella intermedia is a well-known periodontal pathogen in adults, but it has been detected also in the primary dentition of small children ⁵⁶, ⁵⁷. It is frequently recovered from various oral purulent infections in children and also in secondary nosocomial infections ⁵⁸, ⁵⁹. Of note, Prevotella intermedia is always associated with other pathogens and it has never been reported as a monoinfecting agent. Therefore, the proliferation of Prevotella intermedia in noma lesions seems to be the consequence of changes in local ecological conditions due to the development of the disease. These findings invalidate the existence of a single noma pathogen and tend to reconsider noma as a multifactorial, opportunistic disease developing in a relatively normal oral flora in children suffering from chronic malnutrition ⁵³.

Risk factors for cancrum oris or noma

Several risk factors are associated with the pathogenesis of cancrum oris or noma. Reported risk factors for the development of cancrum oris or noma is severe malnutrition, especially protein-calorie malnutrition ¹⁹, ⁴², ³⁶, ⁴⁶, ⁴⁰, ⁶⁰, ⁶¹, ⁶². Other factors that significantly contribute to the pathogenesis of cancrum oris or noma include:

• Comorbidities either at the time of noma diagnosis or in the three months leading up to diagnosis ¹⁹, ⁴², ³⁶, ¹⁸, ⁴⁵, ⁴⁶, ⁴⁸, ⁴⁰, ⁶⁰, ⁶¹, ⁶³, ⁶².
  • Reported comorbidities in the primary studies (case control, cohort, retrospective chart reviews) include malnutrition, respiratory disease ⁴⁷, ⁴⁰, diarrhea ⁴², ⁴⁰, malaria ⁴⁷, ⁶¹ and vaccine preventable diseases, specifically measles ⁴², ⁴⁸, ⁶¹.
  • Recently, an increased incidence of noma has been reported in higher resource settings in patients with immunosuppressive diseases such as human immunodeficiency virus (HIV) ¹³, ¹⁴, ¹⁵, ¹⁶, ¹⁷, ⁶⁴, ⁴⁷, ⁶³.
  • Most of the case reports and case series (n = 68) list at least one comorbidity (103 comorbidities listed in these case reports and case series). The most widely reported comorbidities in the case reports and case series included in a review were malnutrition, HIV, anemia and measles ³.
• Low vitamin A and vitamin C levels ³⁵
• Being between two and five years of age ¹⁹, ⁴², ¹⁸, ⁴⁵, ⁴⁶, ⁴³, ⁴⁸, ⁶¹
• Not being breastfed ⁶⁰, ⁶⁵
• Lack of access to basic health care ¹⁸
• Lack of childhood vaccinations ⁶⁶, ⁶⁵
• Poor oral hygiene practices leading to gingivitis (Stage 0 noma) ⁶⁶
• Low socioeconomic status ⁴⁷
• Lack of variety in the diet ⁶⁵
• Mother being unmarried, not the primary caretaker ⁶⁵ and having a high number of previous pregnancies ⁴⁰ and the absence of chickens at home ⁴⁰

Other studies have hypothesized further risk factors for noma development include:

• Proximity of livestock to living areas and poor sanitation ⁶⁶, which is thought to lead to possible contamination of water and food sources and consequently increasing the risk of infections ⁶⁷, ⁶⁸.

However; caution is needed when interpreting these findings as they are based solely on case reports and case series, primarily reported from health care centers, no causal link or strength of association can be measured. Infections are usually the product of a compromised host and a single offending agent or multiple offending agents. Due to challenges with conducting scientifically robust risk factor analysis for noma, it is difficult to separate comorbidities from predisposing conditions and true causative factors ³, ⁶⁹.

Cancrum oris symptoms

Cancrum oris or noma causes sudden tissue destruction that rapidly gets worse. First, the gums and lining of the cheeks become inflamed, swollen and develop sores (ulcers) ¹⁹, ⁷⁰, ²⁶, ¹, ². These ulcers spread rapidly to the skin, and the tissues in the lips and cheeks die. This can eventually destroy the soft tissue and bone. The destruction of the bones around the mouth causes deformity of the face and loss of teeth ¹⁹, ⁷⁰, ²⁶, ¹, ². The color of the oral cavity may also change into a greyish color. The ulcers develop a foul-smelling drainage, causing bad breath and skin odor. Affected children that survive cancrum oris or noma are often left with serious aesthetic and functional consequences including disfigurement and impairments in breathing, swallowing, speaking and vision that further contribute to their social isolation, stigmatization and discrimination.

Noma can also affect the genitals, spreading to the genital skin this is sometimes called noma pudendi.

Noma stages

For the purposes of early detection, the World Health Organization (WHO) divides cancrum oris or noma into 5 clinical stages ¹, ²:

• Stage 0 – Gum inflammation (simple gingivitis);
• Stage 1 – Acute necrotizing gingivitis;
• Stage 2 – Edema;
• Stage 3 – Gangrene;
• Stage 4 – Scarring;
• Stage 5 – Complications.

The first 4 stages (Stage 0 to 4) are the acute stages of noma lasting only a few weeks. Deaths in noma patients are primarily reported to be due to starvation, aspiration pneumonia, respiratory insufficiency or sepsis ²², ²³, ⁷.

Stage 0 Warning Signs

Before the development of noma, there may be simple gingivitis: inflammation and reddening of the gums which bleed when touched or during brushing of the teeth. The WHO recommends disinfectant mouthwash; if not available, use warm, salted water that has been boiled ¹, ². A high-protein diet, Vitamin A supplements, and patient education on oral hygiene are also recommended to prevent noma from progressing to the acute stages ¹, ².

Stage 1 Acute necrotizing gingivitis

Acute necrotizing gingivitis (ANG) is the first stage of noma ⁷¹, ⁷². The gums are red or reddish-purple and bleed spontaneously ². Acute necrotizing gingivitis (ANG) is characterized by spontaneous bleeding, ulceration of the gingival papillae, pain and sometimes, greyish pseudomembranes ⁷³, ⁷⁴, ¹. The child has foul smelling breath and may drool. Painful ulcers of the gums develop, causing trouble eating. If the patient is malnourished and has recently been sick with an infectious disease, such as measles or chickenpox, they are at more risk for developing noma. Fever may develop at this stage, which can persist indefinitely. Without treatment, acute necrotizing gingivitis (ANG) may evolve into a necrotizing stomatitis and result in the destruction of the attached gingival mucosa, the surrounding oral mucosa, and the underlying bone (Figure 1B). This stage requires antibiotic treatment can halt the disease ¹, ². If no treatment is undertaken, the risk of progression toward noma is very high ⁷⁵.

Figure 1. Acute necrotizing gingivitis

Footnotes: (A) Acute necrotizing gingivitis and (B) necrotizing stomatitis. (A) Acute necrotizing gingivitis (ANG) is considered as an important precursor of noma and is characterized by spontaneous bleeding, ulceration of the papillae, and gingival pain. In this patient, acute necrotizing gingivitis (ANG) of the upper right dental arch is accompanied by an abundance of calculus and plaque, greyish pseudomembranes and disappearance of gingival papillae. (B) Upper right dental arch: necrotizing stomatitis with destruction of gingival papillae and attached mucosa. Presence of greyish pseudomembranes and exposure of alveolar bone. The lesion shows destruction of gingival mucosa and underlying necrotic bone, a likely precursor of noma.

[Source ⁷ ]

Stage 2 Edema

The starting point of noma is defined when facial edema appears in addition to intraoral necrotizing stomatitis (see Figure 2 ), accompanied by a typical halitosis often considered as pathognomonic. This stage is short and lasts only a few days.

This stage begins the acute phase of noma. The telltale sign is facial edema (swelling) of the lips, cheeks, eyes, etc. Ulceration of the gums worsens during this stage; ulceration may spread to the mucosa (soft, mucus-producing tissue) of the mouth and nose. The patient may feel pain or soreness in their mouth and cheeks. Other symptoms at this stage include fever, drooling, fetid breath, lymphadenopathy (swollen lymph nodes), and difficulty eating. Progression of the disease can be halted with appropriate treatment ¹, ².

Figure 2. Stage 2 Noma edema stage

Footnote: Stage 2 edema stage in a child with discolored and brittle hair, a secondary sign of malnutrition.

[Source ⁷ ]

Stage 3 Gangrene

At this and subsequent stages, although the disease can still be treated, complications will inevitably set in. In this stage, the infection eats away at the soft tissue of the patient’s face. The gangrene may affect the cheeks, lips, nose, mouth, and nasal and oral cavities. A peculiarity of this gangrene is that it appears to have a self-limiting character ending in a well-demarcated necrosis. Dead tissue sloughs away over time, leaving holes in the face and the soft tissue, possibly exposing bones and teeth. The patient is apathetic, has little appetite, and has great difficulty eating ¹, ². At this stage, there is a high risk of sepsis leading to death ²², ²³, ⁷.

On some occasions, the body appears to be able to resist and halt the expansion of the gangrene at a certain stage ⁷. Interestingly, some children do not receive treatment and develop relatively small lesions, while others experience huge facial destruction despite appropriate medical treatment ⁷. This may be due to differences in the degree of impairment of their immune systems ⁷.

Stage 4 Scarring

The acute phase is over by this point, but the patient’s life is still at risk and treatment is still recommended. This stage lasts one to two weeks. The patient may experience trismus (difficulty moving/opening the jaw), scars will form, and any exposed teeth will set in place ¹, ².

Stage 5 Complications

The disease is over by this point, but consequences from the gangrenous and scarring stages remain. Tissue may be missing, teeth may still be exposed, and the face is disfigured. The patient may have difficulty eating, drinking, and speaking. Teeth may become set in the wrong places, or be lost altogether. There may still be problems with drooling and with opening/closing the jaw. Reconstructive surgery is an option at this phase. Social reintegration is also very important ¹, ².

Cancrum oris diagnosis

A physical examination is done initially to check for inflamed mucus membranes, oral cavity ulcers, and skin ulcers. This is followed by taking a detailed medical history of the patient.

X-ray, MRI, or CT scans of the jaw, head, and neck can also be done to check the extent and severity of the damage.

Bacterial culture analysis using oral swabs can be done to detect the causative species. In some special cases, biopsy of the oral tissue is also performed.

Blood tests are recommended to determine the immune system functioning.

Cancrum oris treatment

Treatment with broad-spectrum antibiotics, wound cleaning and debridement, hydration and nutritional support and treatment of concomitant diseases such as pulmonary and gastrointestinal infections, malaria, and HIV in the early, reversible stages of cancrum oris or noma can reduce the duration and severity of the acute phase of noma and the extent of tissue damage, therefore reducing mortality and morbidity of noma ²⁴, ⁷⁶, ⁴³, ⁷⁷, ⁷⁸, ⁷⁹, ⁸⁰, ³⁶, ⁷⁷, ²², ⁷⁶, ⁴³. A range of antibiotics were reported in the studies include amoxicillin ⁸¹, ⁸², ⁷⁷, ⁸, metronidazole ⁸³, ⁸⁰, ³⁷, ⁸², ⁸⁴, lincomycin ⁸⁵ and cefotaxime ⁸³, ⁸⁶. No studies comparing the relative efficacy of these antibiotics were identified.

Acute phase treatment (Stages 0 to 4)

The current WHO guidelines for the management of the acute stages of noma in clinical settings includes ¹, ²: oral hygiene (mouth wash Chlorhexidine 0,2%, 10 ml), antibiotic treatment (amoxicillin and metronidazole), nutritional support (high protein), wound cleaning (compresses soaked in hydrogen peroxide) and dressing (honey for local dressing and for antibacterial action and regeneration) ¹, ².

A range of antibiotics were reported in the studies include amoxicillin ⁸¹, ⁸², ⁷⁷, ⁸, metronidazole ⁸³, ⁸⁰, ³⁷, ⁸², ⁸⁴, lincomycin ⁸⁵ and cefotaxime ⁸³, ⁸⁶. No studies comparing the relative efficacy of these antibiotics were identified.

Complications treatment

If the patient survives the acute illness, they can live into adulthood but often require extensive reconstructive surgery and intensive physiotherapy to improve the resulting structural and functional defects that often require a number of surgical treatments ⁸⁷, ⁸⁸. Studies have highlighted the fact that the time between acute illness and surgical care can be decades ²⁵, ⁸⁹, ²⁸. The clinical manifestation of each noma case is unique, and as such, the surgical procedures used to treat each noma case differ ³.

Reported surgical techniques include pedicled supraclavicular flaps for the treatment of large unilateral facial defects ⁹⁰, ⁹¹; myocutaneous submental artery flaps, bony and/or soft tissue trismus releases ⁹², forehead flaps ⁹², ²⁸ and lower lid ectropion release ⁹². In one study, extra-articular ankylosis due to noma was treated using soft tissue reconstruction with large free flaps ⁹³. Trismus was treated using a bone distractor in one study ⁹⁴ and in another mouth opening was performed by bone-bridge excision, sometimes associated with contralateral coronoidectomy ⁹³. In a further study, the reconstruction of an upper lip defect was conducted using Gillies fan flaps ⁹⁵. A 2006 book on noma surgical techniques includes information on the reconstruction of the lips and corner of the mouth using Abbe, Estlander and fan flaps; and the reconstruction of the cheek using temporo-parietal fascia and deltopectoral flaps; and the reconstruction of central defects using radial forearm and local turnover flaps ²⁶. Challenges with anaesthesia for noma survivors have been reported, particularly in patients with severe trismus ⁹⁶, ⁹⁷.

Physical therapy is an essential part of noma treatment, especially to prevent or minimize trismus ⁹⁸ and can lead to improvements in eating, chewing and speaking ⁹⁹.

Noma often leads to stigmatization and resultant social isolation of the patients and their family members from their communities ²⁴. Several studies have highlighted the importance of including social and psychological support for noma patients and their families ²⁵, ⁸⁸, ¹⁰⁰, ¹⁰¹.

Outcomes of noma treatment are difficult to ascertain due to inconsistent patient follow-up in most studies ²⁷. This is mostly due to the remote locations of the home villages of patients and difficulties in accessing health care facilities ²², ¹⁰², ⁷⁸. However, there have been evaluations of noma survivors after surgery which have shown that surgical treatment for noma survivors greatly improves their quality of life, even if functional improvements (specifically mouth opening) are not pronounced ⁹⁰, ²⁵, ⁸⁹, ¹⁰⁰. The extent of long-term consequences and their impact on quality of life of noma patients depends on the severity of the disease at initial presentation, efficacy of antibiotic treatment, wound debridement and the facial structures affected ²⁷, ⁷⁶, ⁴³, ⁷⁷.

Cancrum oris prognosis

In some cases, cancrum oris or noma can be deadly if it is not treated. Other times, cancrum oris or noma may heal over time, even without treatment. However, once noma reaches the gangrenous stage of the disease with a visible hole in the face, it is likely that children who survive will suffer severe facial disfigurement, have severe complications including difficulty eating, seeing, breathing, face social stigma and isolation ¹, ², ²⁴, ²⁵. Only approximately 15% of children survive acute noma ¹⁰³, ¹⁰⁴, ¹⁰⁵. Most survivors present with facial deformities and trismus or ankylosis of the mandible, resulting in eating problems, oral incontinence, speech difficulties, and social isolation  ⁷.

Survivors often need complex reconstructive surgery to restore form and function ²⁶. Trismus (a restriction in mouth opening) is one of the most disabling complication ²⁷, ²⁸ and can lead to complications such as aspiration, malnutrition, poor oral hygiene, speech deficits, a compromised airway, and pain ²⁹.

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