What Is Granulomatous Cheilitis?

Granulomatous cheilitis, also named cheilitis granulomatosa is a rare, chronic condition or disease that causes persistent/reoccurring painless lumpy swelling of the lips.¹ In most cases, this swelling can be cosmetically very disturbing and can affect both upper (top) and lower (bottom) lips.^1,2

The exact cause of it may be unknown or difficult to diagnose, in some cases, other symptoms may also be noted which may be limited to the mouth or may affect the face or the whole body such as gastrointestinal symptoms.²

While not life-threatening, it can majorly affect the patient's quality of life due to severe cosmetic disturbance.² Diagnosis and treatment planning requires dental/medical professionals with specialist expertise; hence, seeking medical attention at the earliest is strongly advised.^1,2

Overview

Cheilitis granulomatosa or granulomatous cheilitis is a lumpy swelling of the lips that occurs or reoccurs generally over a long period of time.¹ This swelling can affect both lips and is commonly painless.¹ It is a rare disease affecting only an estimated 0.08% of the population with onset generally seen in younger adult life in both assigned sexes at birth equally, with some studies reporting a higher number for people assigned female at birth (AFAB).⁵ No predisposition for any race is observed in granulomatouos cheilitis.⁵

Granulomatous cheilitis can be idiopathic (without any specific cause) or related to other health conditions. When it occurs by itself i.e., just swelling of the lips it is called Miescher cheilitis or cheilitis granulomatosa of Miescher.³ It also occurs as part of Melkersson-Rosenthal Syndrome, which includes a classical triad of symptoms mainly affecting the mouth and the face.⁴  Furthermore, it may also be one of the symptoms in more complex conditions that affect the face or other organ systems such as orofacial granulomatosis, Crohn’s disease, sarcoidosis etc.⁵

While it is not life-threatening, it is important to note here that any sudden swelling of the face or lips requires urgent medical attention as it could indicate a serious allergic reaction. But in most cases of granulomatous cheilitis, the swelling develops slowly over a long period of time and mild cases may require only minor interventions such as dietary restrictions.^3,5 Although as is noted more commonly, once persistent granulomatous cheilitis has set in, severe cosmetic disturbances will require medical treatments such as:⁵

• Intralesional injection of corticosteroids like triamcinolone
• Immunomodulatory therapy such as clofazimine or azathioprine

Causes of granulomatous cheilitis

The exact cause of granulomatous cheilitis is not known, however, there are several different aetiologies (causative agents/factors) and causative mechanisms that have been linked to it.^1,6,7 The following are some of them^1,5,6,7,8:

1. Genetic causes: No concrete evidence exists to establish an association, but involvement amongst family members has been noted often, although no actual association with HLA (genes) has been found in patients compared to populations without the condition.¹
2. Immunologic causes: Granulomatous cheilitis is a chronic granulomatous inflammatory condition. Like all granulomatous diseases, it is associated with an altered immune response of the body that results in granulomatous inflammation, which is seen externally as swollen lips.^1,7,8 Certain autoimmune conditions where granulomatous cheilitis may occur are sarcoidosis, amyloidosis, and granulomatosis with polyangiitis.
3. Allergic causes: Allergic reactions to foodstuffs and food additives such as certain benzoates, tomatoes, gluten, cinnamon etc. may trigger an episode of granulomatous cheilitis.^5,1 Certain other products such as toothpaste, cosmetics, or medications may also contain benzoates.⁵ Furthermore, allergic reactions to dental materials, or sensitivity to ultraviolet B (UVB) radiation are suspected as possible triggers.^5,7
4. Infectious causes: Specific infections such as tuberculosis and fungal infections (candida albicans, histoplasmosis) cause a disturbance in the normal immune response of the body leading to granulomatous inflammation.^1,5 Nonetheless, any solid association between these infections and granulomatous inflammation of the lips is yet to be established. ^1,5
5. Crohn’s disease: Many studies and discussions have demonstrated that granulomatous inflammation of the lips may occur as one of the earlier symptoms or in combination with other symptoms of orofacial granulomatosis. By itself, granulomatous inflammation can be an extra-intestinal (outside of the intestines) variant of Crohn’s disease with systemic disease symptoms developing much later.^1,5 In spite of this demonstrated association, less than 1% of patients with Crohn’s disease develop granulomatous cheilitis.^1,5
6. Other causes: The dermatological (skin) condition of rosacea or cancer or infection resulting in obstruction of lymphatics around the lips may also cause granulomatous Cheilitis.

Signs and symptoms of granulomatous cheilitis

Signs and symptoms of granulomatous cheilitis may be quite limited unless accompanied by any other syndromic illness, autoimmune conditions, or Crohn’s disease.

In Miescher cheilitis, granulomas (the inflammation) are confined only to the lips.^5,9  Individuals commonly develop painless, puffy, lumpy lips, which may feel soft, firm, or nodular when touched.⁹ The first episode of swelling of the lips is sudden and in most cases, it resolves or reduces within days or even hours of occurrence.^5,9 Following this, the swelling may keep reoccurring and reducing in a cyclic fashion, repeatedly within a short (days) or long (years) term.⁹

With each repeated episode, the swelling may become larger, and more persistent.⁹ Eventually, due to the persistent lymphoedema (swelling caused by a collection of lymph) and non-caseating granulomatous inflammation, the shape of the lip is permanently changed.⁹ Once this type of painless but permanent swelling is present, over time the lips may appear cracked, and discoloured with a reddish-brown colour (due to repeated cycles of cracking-bleeding-healing), which may eventually become painful.⁹ Additionally, over time the consistency of the lip also becomes hard or rubbery.^1,9

The swelling most commonly involves the upper lip, followed by the lower lip and the cheeks in prevalence.⁹ Other areas of the mouth or the forehead, eyelids, or one side of the scalp may be involved in the swelling by themselves or as part of wider orofacial swelling or orofacial oedema.⁹

Some other common symptoms that might accompany granulomatous cheilitis are:⁹

• Headache
• Fever
• Visual disturbances
• Increase in the size of the lymph nodes (seen in 50% cases)
• Central nervous system defects (severity and association may vary)
• Facial nerve palsy (facial nerve paralysis that is generally seen in 30% of patients with granulomatous cheilitis, it is also seen in patients with Melkersson-Rosenthal syndrome, its presentation varies, developing before or after the swelling)⁹
• Plicated (pleat-like) or fissure tongue (seen in 20-40% of cases, also seen as part of Melkersson-Rosenthal syndrome, it is also called scrotal tongue)
• Splitting of the lips and angular stomatitis/cheilitis

Besides the various symptoms discussed above it should also be noted that granulomatous cheilitis could be accompanied by other symptoms inside the mouth such as linear ulcers, mucosal tags and cobblestoning, which may be a part of orofacial granulomatosis or if gastrointestinal symptoms also exist – oral Crohn’s disease.⁹ Additionally, depending on any underlying pathology (e.g., tuberculosis) further symptoms may also be noted.^1,9

Management and treatment for granulomatous cheilitis

There is no cure for granulomatous cheilitis and most treatments aim to only reduce the intensity of inflammation beneath the lips and the repeated number of episodes of swelling.¹ Thus, most of the proposed treatments are only symptomatic, with the aim of improving the quality of life of patients.¹ Spontaneous reduction or disappearance of this condition is highly rare but still reported in some cases.¹

The simplest and easiest ways of managing milder versions are dietary restriction and avoiding any medicines or cosmetics that may contain irritants such as cinnamon or preservatives such as benzoates.^5,9 Additionally, switching to benzoate-free toothpaste and having any dental filling replaced may be effective in reducing inflammation, although the effectiveness of this differs highly among various individuals.^5,9

The most effective treatment is intralesional (local) injections of corticosteroids (commonly known as steroids) for short courses.¹ Some commonly used steroids are prednisolone and triamcinolone.^1,9 Topical steroid creams, may also be helpful in reducing inflammation in granulomatous cheilitis.

Other treatment options that have been trialled and may be successful include the use of anti-inflammatory or immunomodulatory medicines such as tacrolimus creams or oral tablets of clofazimine.¹ Immune system-suppressing medications such as azathioprine, mycophenolate mofetil, and other biologic agents have been trialled in studies alone or in different combinations, with mixed results which tend to show some positive scope.^1,9

Last but not least, although its use and indications are very rare, the surgical reduction of the size of the lips (cheiloplasty) is an option, although its effectiveness and need are again highly individualistic.^1,5,9

Diagnosis

Diagnosis of granulomatous cheilitis is commonly suspected clinically (in-person) on examination, and through history-taking by an oral medicine specialist or a dermatologist.^5,9 Further confirmation of the diagnosis is established by performing a biopsy (surgically removing a small piece of the lip lesion) for further examination under the microscope by dental professionals specialising in oral pathology.^1,5,9

Additional investigations may be ordered by your doctor to rule out any other diagnoses or underlying conditions such as:^5,9

• Blood tests
• Different imaging scans such as radiography
• Endoscopy
• Biopsy of different areas in the body
• Tuberculin test
• Allergy patch tests

Some differential diagnoses of granulomatous cheilitis are angioedema, Crohn’s disease, cheilitis glandularis, dental abscess, orofacial granulomatosis, granulomatosis with polyangiitis, tuberculosis, sarcoidosis, leprosy, leishmaniasis, fungal infections, exfoliative cheilitis.^1,5,9

FAQs

How can I prevent granulomatous cheilitis?

It cannot be prevented although intensity and frequency can be reduced by following dietary restrictions, avoiding the use of specific products that contain preservatives/irritants, being regular with your medication/prescribed treatment and visiting your treating clinician.^1,9

How common is granulomatous cheilitis?

It is a rare disorder that has been estimated to affect only about 0.08% of the general population. However, these figures are not completely reliable since the rarity of the condition limits the data available on it to derive such calculations.¹

Who is at risk of granulomatous cheilitis?

Granulomatous cheilitis can occur in all races and age groups but is noted most commonly among younger adults aged between 20-40 years of age.¹ Reports of diagnosis among children although present are rare.¹ Some studies report possibly higher numbers of assigned females at birth.^1,5 Some rare cases of familial risk have also been reported.¹

When should I see a doctor?

Any sudden swelling in the face or lips needs urgent medical attention but in most cases, since the onset of swelling might be over a long period of time, it is advisable to visit a doctor or dentist if you note any of the signs and symptoms discussed above.^1,5,9

Summary

Granulomatous cheilitis is a rare, chronic condition that causes painless lumpy swelling of the lips.¹ it is estimated to affect about 0.08% of the general population.^1,5 The exact cause is unknown, although a number of causative agents to name a few – genetic factors, Crohn’s disease, and infections such as tuberculosis have been associated with it.^6,7 It may or may not be accompanied by any other signs and symptoms depending on the underlying causative agent.¹ Its diagnosis commonly requires a biopsy and histopathological (under the microscope) examination along with some further testing to rule out any other causes.⁹ Common treatment options include corticosteroids, immune system modifying or suppressing medication, dietary restriction, avoiding items containing preservatives or irritants and surgery. It is not life-threatening, but it cannot be cured, tends to persist throughout life and impacts the quality of life severely.^1,9