[MIM 181 000, 612 387, 612 388]

(Besnier-Boeck-Schaumann's disease, BBS, benign lymphogranulomatosis))

Variable incidence: in Europa,there is a north-south gradient (640 per 100,000 inhabitants in Sweden compared to 0.4 per 100,000 in Spain). In  France,the prevalence is 10 per 100,000 inhabitants. Frequency peak: between 30 and 40 years of age but pediatric cases are described. More common in the black population, where it is also more common in women and often more severe.   Systemic inflammatory disease  of unknown cause that preferably affects the pulmonary interstitium, but can reach other organs, including the skin or lymph nodes (mediastinum).

The evolution is generally benign; it heals spontaneously except in 20 % of patients in whom it causes respiratory complications by progressing to pulmonary fibrosis.

The causes are unknown.  Some factors are:

-        inhalation of dust  or certain particles

-        the presence of antibodies  against of the Borrelia bacterias is often found suggesting that Lyme disease  (following a tick bite) may be a cause or a contributing factor.

-        there is probably a genetic factor: there are familial cases and the risk increases fivefold if a close family member is affected. Various forms have been identified:  SS1, autosomal dominant transmission of a susceptibility gene (HLADRB1) on 6p21.32 [MIM 181,000]; SS2, autosomal dominant transmission of a susceptibility gene (BTNL2) on 6p21.32 [MIM 612387]  and  SS3, transmission of a susceptibility gene (ANXA11) on 10q22.3 [MIM 612 388]. The severity of the disease also appears to depend on certain  HLA  groups, those with HLA-DRB1-03 having forms with spontaneous healing, and those with HLA-DRB1-14 or HLA-DRB1-15, more chronic forms.

The mechanism of the disease probably involves cellular immunity  against an antigen in a predisposed genetic field. One of these antigens could be  mycobacterial, as mycobacterial DNA is frequently associated with sarcoidosis and a mycobacterial catalase-peroxidase is identified in 50 % of cases. The chronology of sarcoid inflammation has been well studied in the lung. There are three successive phases: lymphocytic and macrophagicalveolitis,  the granulomatous phase, and finally  fibrosis  (optional).

1. lymphocytic and macrophagic alveolitis: activated CD4 lymphocytes concentrate in the alveoli of the lung, causing alveolitis. These lymphocytes secrete pro-inflammatory mediators such as interleukin 2 and the chemotactic factor of MCP-1 monocytes; they also cause activation of B lymphocytes, which produce gammaglobulins; activated macrophages  are attracted by the activation of the CD4 lymphocytes.
2. the granulomatous phase: activated macrophages accumulate in the lung. They secrete the angiotensin conversion enzyme  and form  tuberculoid  granulomas;  tuberculinic anergia is commonly associated with lymphopenia but there is no immunodepression
3. fibrosis: granulomas cause pulmonary fibrosis,the main pulmonary complication of sarcoidosis

Clinical presentation:

• lung disease is almost constant, but it is symptomatic in only 1/3 of cases
• adenopathies (30 %)
• skin damage: erythema nodosum
• eye damage (10-25 %): conjunctivitis, anterior granulomatous and / or posterior exudative uveitis, nodules of the iris
• non-specific arthralgias.
• heart disease (40 %): often asymptomatic, sometimes faintness, heart failure; echocardiography and MRI
• laryngeal involvement (10-15 %): hoarseness, laryngotracheal dyspnea, dysphagia, oropharyngeal pain, snoring.
• hypercalcemia (5 %)
• liver damage (20 %) usually asymptomatic
• neurological involvement: rotary vertigo, loss of balance

In its typical form, the Lofgren syndrome which combines erythema nodosum, polyadenopathies and diffuse joint pain, is sufficient to make the clinical diagnosis of sarcoidosis.

The diagnosis of sarcoidosis is often difficult and late: it is based on various signs:

• clinical: signs presented by the patient (often none);
• radiological: there are four stages:
• stage 1: bilateral and symmetrical mediatinal adenopathies,
• stage 2: mediastinal adenopathies and interstitial infiltrates/micronodules,
• stage 3: interstitial infiltrates/micronodules without mediastinal adenopathies,
• stage 4: fibrosis.
• biological: absence of inflammatory syndrome (except cases of Lofgren syndrome),  lymphopenia, hypercalcemia and hypercalciuria, increased levels of ACE (angiotensin conversion enzyme)
• histological: a biopsy  of a  granuloma  is necessary to make the diagnosis, unless there is a Lofgren syndrome that is sufficient to make the diagnosis. The most easily accessible lesion is used (skin, salivary gland, adenopathy, bronchi) the microscopic study of which objectivates an epithelioid  and gigantocellular granulomatous tissue without caseous necrosis. In the absence of easily accessible lesions, mediatinoscopy may be proposed, but it may be replaced by a biopsy by bronchial fibroscopy  and endobronchial echoguided biopsy
• bronchoalveolar lavage showing a CD4 lymphocytic hyperlymphocytosis  in the pulmonary alveoli with a  CD4/CD8 ratio greater than 3.4.
• functional breathing tests are helpful to assess the severity, the impact of lung damage and the evolution.
  Typically:

-        normal spirometry or restrictive syndrome,

-        a normal blood  gases, but desaturation during a stress test, sometimes hypoxemia and hypocapnia in severe forms,

-        lowered DLCO and decreased DLCO / alveolar volume ratio

Evolution: spontaneous healing in the majority of cases, especially the asymptomatic forms.

Treatment: severe symptomatic forms require a treatment.

The most commonly used treatment is local (inhaled corticosteroids, locally for anterior uveitis or by  injection for posterior uveitis) or systematic corticotherapy. Corticosteroid treatment is extended for at least 2 years at the initial dose of 0.5 mg/kg/day of prednisolone  (sometimes up to 1 mg/kg/day). The doses are then very slowly decreased, with possible relapses when doses become less than 0.15 mg per day and at the end of treatment. In some cases, corticosteroid therapy can be associated with  methotrexate. Alternative treatment are immunosuppression (thalidomide,  methotrexate, azathioprine), chloroquine, antibodies directed against TNF  (infliximab, etanercept or adalimumab).

Anesthetic implications:

see thorax RX and liver enzymes; eye protection; side effects of the ongoing treatment

References :

-        Hong SA, Bell JR.
Progressive upper airway obstruction and dysphagia in a child with supraglottic edema.
JAMA Otolaryngology-Head & Neck Surgery 2020 ; September (in press)

Updated: September 2020