Sarcoidosis - Oral Mucosal Lesion
There are numerous subtypes of cutaneous sarcoidosis exhibiting many different morphologies. Lesions are broadly categorized as either specific granulomatous lesions or nonspecific lesions:
- Specific lesions, all of which histologically contain noncaseating granulomas, consist of macules, papules, plaques, nodules, hypopigmented sarcoid, lichenoid sarcoid, lupus pernio, scar sarcoidosis, alopecia, ulcers, subcutaneous sarcoid, ichthyosiform sarcoid, nail dystrophy, and other rare forms. In general, these lesions are asymptomatic; however, pruritus may be present in 10% to 15% of patients.
- Nonspecific lesions, such as erythema nodosum, represent a reactive process and do not contain granulomas histologically.
Specific sarcoidosis syndromes include Heerfordt syndrome and Löfgren syndrome. Heerfordt syndrome is characterized by the combination of chronic inflammation of the parotid glands and lacrimal glands, subfebrile temperatures, and cranial nerve palsies. Löfgren syndrome is sarcoidosis that presents with bilateral hilar lymphadenopathy, erythema nodosum, and arthritis. Similar to sarcoid-associated erythema nodosum, the presence of Löfgren syndrome implies a good prognosis.
The etiology of sarcoidosis has not yet been elucidated; however, numerous theories have been proposed. Various environmental exposures to chemical and metal materials, exposures to water damage or high humidity in the workplace, infectious agents such as Mycobacterium tuberculosis, and autoimmune processes have been hypothesized to be potential causes. It is unclear whether socioeconomic status may play a role in these possible exposures. Given the multiple environmental risk factors that have been reported, it has been suggested that the development of sarcoidosis probably depends on immune responses to various ubiquitous environmental triggers. Hence, it is not surprising that genetic predisposition seems to play a role. Specifically, HLA class II antigens, encoded by HLA-DRB1 and DQB1 alleles, have consistently been associated with sarcoidosis. Also, genomewide scans have shown linkage signals at chromosomes 3p and 6p in white Germans and strong signals at chromosomes 5p and 5q in African Americans. Subsequent fine-mapping studies of African Americans suggest that sarcoidosis susceptibility genes may exist on chromosomes 3p and 5q11.2, while protective genes may be present on a region of 5p15.2. Thus it seems reasonable to propose that susceptibility to sarcoidosis likely depends on genetically determined immune responses to environmental exposures. Whatever the true underlying etiopathogenesis, the immunopathogenesis of sarcoidosis is known to involve the activation of alveolar macrophages and T-cells, leading to inflammation and, ultimately, granuloma formation.
Some drugs and exposures have been associated with the development of sarcoidosis and sarcoid-like granulomatosis. Patients undergoing antiviral therapy for chronic hepatitis C – both monotherapy with interferon (IFN)-alpha and combination therapy with IFN-alpha and ribavirin – have developed new-onset sarcoidosis or experienced re-activation of preexisting sarcoidosis during or shortly after treatment. The disease typically manifests as pulmonary and/or cutaneous sarcoidosis and follows a benign course, resolving spontaneously or within months after antiviral treatment is completed. More complicated multisystem cases, eg, involving the CNS, have been reported. The use of systemic corticosteroids to treat sarcoidosis in such patients should be considered with caution due to their adverse effects on viral loads. In addition, there have been an increasing number of reports of new-onset sarcoidosis manifesting in patients who are receiving anti-tumor necrosis factor (TNF)-alpha therapy (etanercept, infliximab, adalimumab), eg, for a rheumatologic diagnosis. This is paradoxical, because TNF-alpha inhibitors have been used to treat sarcoidosis with some success. Disease typically resolves with discontinuation of the drug and steroid therapy. It has been reported that exposure to moderate to high levels of silica increases the risk for sarcoidosis. This association is more common in males due to occupational exposure.
Sarcoidosis occurs throughout the world in people of all ages and ethnicities and in both sexes, with a slight female predominance. Incidence peaks between the 2nd and 3rd decades, with a second peak occurring in Scandinavian and Japanese women over the age of 50. The incidence and severity of sarcoidosis vary greatly between different regions and ethnicities, probably because of differences in environmental exposures, surveillance methods, and genetic factors. Some data suggest that patients with darkly pigmented skin are up to 17 times more commonly affected with sarcoidosis than white patients in different parts of the world.
There is an ethnic difference in incidence in the US population. The annual age-adjusted incidence of new cases is highest in African American females (39.1 per 100,000), followed by African American males (29.8 per 100,000) and then white females (12.1 per 100,000); it is lowest in white males (9.6 per 100,000). Overall, African Americans have about a 3- to 4-fold higher incidence of sarcoidosis compared with whites. In general, sarcoidosis has been noted to be most common in African Americans. Also, sarcoidosis tends to be more severe, extensive, and progressive in this population; there is more frequent involvement of the eyes, liver, bone marrow, extrathoracic lymph nodes, and skin in African Americans compared with whites, and they have a lower likelihood of clinical recovery compared with whites, particularly in the presence of extrathoracic involvement.
The European prevalence is estimated at 40 cases per 100,000, with northern European countries reporting higher incidences than southern European countries. The prevalence in India has been estimated to vary from minimal to 150 cases per 100,000. In a 2008 study of patients in Tunisia, sarcoidosis was found to be much more frequent, extensive, and severe in black West Indian, African, Indian, and Pakistani patients than in native white patients. Sarcoidosis appears to be rare in East Asians, and specifically cutaneous sarcoidosis is rare in Asia.
Pediatric Patient Considerations:
Sarcoidosis is an uncommon disease in pediatric patients and is extremely rare in children younger than 6 years. In adolescents, the cutaneous manifestations of sarcoidosis are similar to those seen in adults, with the exception of lupus pernio and erythema nodosum, which are rare in that age group.
Although rare, when sarcoidosis presents in children younger than 6 years, it is characterized by a triad of skin rash, uveitis, and arthritis without intrathoracic involvement.
D86.3 – Sarcoidosis of skin
31541009 – Sarcoidosis
- Allergic contact dermatitis
- Ascher syndrome – Inherited condition with swelling of lips and eyelids.
- Cheilitis granulomatosa – Isolated granulomatous inflammation of the lip(s) without facial palsy or fissured tongue.
- Crohn disease – Granulomatous cheilitis in the setting of Crohn gastrointestinal disease.
- Hemangioma – Present in infancy. May regress, leaving a fat pad.
- Oral lichen planus