The diagnosis of sarcoidosis is often delayed for months to years because symptoms are nonspecific and can relate to involvement of any organ.22
Thirty to sixty percent of patients with pulmonary sarcoidosis are asymptomatic.23 Other than the lung, the skin, eye, liver, and peripheral lymph nodes are commonly involved. Consequently, sarcoidosis should be considered in a patient with skin lesions and concomitant pulmonary symptoms, eye complaints, right upper quadrant abdominal pain, or peripheral lymphadenopathy. In addition, the cytokines associated with the granulomatous inflammation of sarcoidosis may cause constitutional symptoms such as fever, night sweats, malaise, and weight loss.
Cutaneous lesions of sarcoidosis may occur before, coincident with, or after systemic involvement. Specific cutaneous lesions are usually asymptomatic. Pruritus and pain are rare. Cosmetic disfigurement is the most common complaint. Erythema nodosum associated with sarcoidosis is indistinguishable from erythema nodosum unassociated with sarcoidosis (see Chapter 70).
Classically, lesions are divided into two categories: (1) specific and (2) nonspecific. Specific lesions have granulomas on biopsy. Nonspecific skin findings are reactive and do not exhibit sarcoidal granulomas.
Specific sarcoidal lesions most often are found on the head and neck (Figs. 152-2, 152-3, and 152-4) but may occur symmetrically or asymmetrically on any part of the skin and mucosa. Almost all morphologies have been reported, including macules, papules, patches, plaques, and nodules. Alopecia occurs with scalp involvement, and nail changes also occur. Specific lesions of sarcoidosis may be scaly, telangiectatic, or atrophic. Despite the diversity in appearance, there are several clinical presentations that are classically associated with cutaneous sarcoidosis.
Cutaneous sarcoidosis of the face. Micropapular form.
Cutaneous sarcoidosis of the face. Papular form. Some of the papules have enlarged to small plaques.
Cutaneous sarcoidosis of the face. Symmetric papules on cheeks.
The most common presentation is the papular form (see Figs. 152-2, 152-3, and 152-4). These firm, 2–5-mm papules often have a translucent red-brown or yellow-brown appearance. The yellow-brown color has been likened to “apple jelly” and is accentuated with diascopy (Fig. 152-5). In addition to the color change, the underlying granulomas have a nodular quality that can also be appreciated with diascopy. The apple jelly appearance and nodules are not pathognomonic for sarcoidosis, as other granulatomous skin conditions, such as lupus vulgaris (see Chapter 184), may exhibit similar diascopic properties. Epidermal changes may or may not be present, but often the lesions have a waxy appearance, which reflects mild epidermal atrophy. Papular lesions occur most commonly on the face and neck, with a predilection for periorbital skin (see eFig. 152-5.1). Annular plaques (Fig. 152-6), nonannular plaques (Fig. 152-7 and see eFig. 152-7.1), and nodules (Fig. 152-8) may develop from these papular lesions and may or may not retain the classic translucent quality of the papules.
Diascopy highlights the “apple jelly” coloration of cutaneous sarcoidosis.
Periorbital distribution of sarcoidosis.
Cutaneous sarcoidosis with an annular configuration.
Plaques of cutaneous sarcoidosis on the neck and upper back.
Cutaneous sarcoidosis on the posterior arm.
Nodular sarcoidosis in the face. In Caucasians, lesions of sarcoidosis are often red or purple.
Lupus pernio describes the relatively symmetric, violaceous, indurated plaques and nodules that occur on the nose, earlobes, cheeks, and digits (Figs. 152-9, 152-10, and 152-11). This clinical variant of sarcoidosis is distinctive and has been associated with systemic involvement. Lupus pernio is associated with a higher prevalence of upper respiratory tract disease.24 Lupus pernio lesions may directly extend into the nasal sinus, leading to epistaxis, nasal crusting, and sinus bone involvement.
Lupus pernio along the nasal rim. This patient also had sarcoidosis of the upper respiratory tract (SURT) (see Section “Other Organs”).
Violaceous lupus pernio lesions on cheek and nose.
Violaceous lupus pernio on distal fingers.
Angiolupoid lesions are pink papules and plaques with prominent telangiectasias that usually occur on the face (see eFig. 152-11.1) and may be a variant of lupus pernio, as both lesions usually appear on the face and can be violaceous.25,26 However, angiolupoid lesions tend to be less numerous than the papular and lupus pernio forms.26
Angiolupoid lesions on the cheeks and nose.
Rarely, sarcoidosis can present as persistent subcutaneous nodules (Darier-Roussy sarcoid).27 The nodules may be tender or painless and preferentially occur on the extremities.
Cutaneous sarcoidosis occurs preferentially within scar tissue, at traumatized skin sites, and around embedded foreign material such as silica. Scars become inflamed and infiltrated with sarcoidal granulomas (Fig. 152-12). Inflammation of old scars (see eFig. 152-12.1) may parallel or precede systemic disease activity. Infiltrated scars may be tender or pruritic. Scar sarcoidosis may be the only cutaneous finding in a patient with systemic sarcoidosis; therefore, it is important to closely examine scar tissue in patients suspected of having the disease. The presence of sarcoidal granulomas surrounding foreign material does not establish the diagnosis of sarcoidosis, nor does foreign material in the presence of granulomas exclude the diagnosis.28 Other signs of systemic or cutaneous involvement are required to confirm the diagnosis.
Sarcoidosis arising in old facial scars sustained after car accident.
Sarcoidosis arising in an old surgical scar.
Alopecia occurs with involvement of the scalp and may be scarring or nonscarring (see eFig. 152-12.2).29–32 Biopsy shows noncaseating granulomas. Its reversibility is dependent on the degree of destruction of hair follicles.
Discoid sarcoidal plaque on the forehead and scalp leading to alopecia and simulating a discoid lesion of chronic cutaneous lupus erythematosus.
Sarcoidosis may cause nail plate deformation and discoloration, but the incidence is very low.33 There may be clubbing, (Fig. 152-11) subungual hyperkeratosis, and even nail plate destruction. Nail manifestations may result from granulomas in the nail matrix or from involvement of adjacent bone.
Sarcoidal granulomas may cause papules and plaques of the mucosal surfaces and tongue. Sarcoidosis is one cause of Mikulicz syndrome, the bilateral enlargement of the lacrimal (see eFig. 152-12.3), parotid, sublingual, and submandibular glands.
Lacrimal gland enlargement in a patient with sarcoidosis.
A myriad of additional clinical presentations have also been reported. These include ichthyosis,34 erythroderma,29 ulcerations (see eFigs. 152-12.4 and 152-12.5),35 morphea-form plaques,36 lichen niditus-like papules,37 folliculitis-like lesions,38 psoriasiform plaques,39 hypopigmented areas,40 gyrate erythema,41 verrucous lesions,38 faint erythema, penile (see eFig. 152-12.6) and vulvar lesions,42,43 palmar erythema,44 discoid lupus-like plaques,45 lower extremity edema,46 lesions mimicking tuberculoid leprosy (see eFig. 152-12.7) polymorphous light eruption,38 and pustular lesions.38
Ulcerative lesions of sarcoidosis.
Cutaneous sarcoidosis. Penile lesions.
Dermal plaque with no epidermal involvement mimicking tuberculoid leprosy.
Erythema nodosum (see Chapter 70) is the main nonspecific cutaneous manifestation of sarcoidosis (prevalence of approximately 17%). Erythema nodosum with bilateral hilar adenopathy, arthralgias, and fever is frequently the initial manifestation of sarcoidosis and is called Löfgren syndrome. These patients tend to have an acute form of sarcoidosis with eventual resolution.
Other nonspecific cutaneous manifestations of sarcoidosis are much less common. The neutrophilic dermatoses, Sweet disease and pyoderma gangrenosum, have been reported as nonspecific cutaneous sarcoid lesions. Most of the sarcoid patients with Sweet disease lesions or pyoderma gangrenosum have concomitant erythema nodosum.47 Nonspecific erythematous eruptions resembling viral exanthems or drug reactions without histologic evidence of granulomatous inflammation occur rarely with acute sarcoidosis. Additionally, patients with sarcoidosis may have pruritus without granulomatous infiltration, leading to prurigo nodules.25 Erythema multiforme had been regularly cited as a nonspecific cutaneous manifestation of sarcoidosis,38 but reports of histologically proven erythema multiforme with interface dermatitis associated with sarcoidosis are virtually nonexistent in the literature,25,38,48,49 and any association is probably coincidental. Erythroderma and lower extremity swelling have been described as both specific and nonspecific lesions of sarcoidosis.25,46,50,51
Related Clinical Findings
The lung is the most common organ involved with sarcoidosis. Findings on pulmonary examination are usually absent. Patients with pulmonary sarcoidosis are often asymptomatic, with the disease detected on a screening chest radiograph. Common symptoms include dyspnea, cough, chest pain, and wheezing. The chest radiograph is abnormal in more than 90% of patients with sarcoidosis. Bilateral hilar adenopathy is noted in 50%–85% of cases (see eFig. 152-12.8). Pulmonary parenchymal infiltrates are seen in 25%–60% of cases.
Sarcoidosis stage 2 chest radiograph showing bilateral interstitial parenchymal infiltrates, bilateral hilar adenopathy, and right paratracheal adenopathy.
Chest computed tomography (CT) reveals more thoracic disease than can be appreciated on the chest radiograph. CT is superior to the chest radiograph in detecting thoracic involvement with sarcoidosis, but there is insufficient evidence that CT has a clinical role in the management of pulmonary sarcoidosis.52
In sarcoidosis patients with normal lung parenchyma on chest radiograph, pulmonary function tests are abnormal in 20%–40% of cases. When the chest radiograph is abnormal, pulmonary function tests are abnormal in 50%–70% of cases.
The eyes are involved in one-fourth to three-fourths of sarcoidosis patients.53 Eye involvement with sarcoidosis is potentially vision threatening, and the patient may be asymptomatic. For this reason, every patient diagnosed with sarcoidosis requires an ophthalmologic examination.53 Redness, burning, itching, or dryness are the most common ocular symptoms when present. Any portion of the eye may be involved, and eye involvement may be the first manifestation of the disease.53 Uveitis is the most common ocular manifestation and can lead to cataracts and glaucoma. Other ocular manifestations include conjunctivitis, lacrimal gland involvement causing kerato-conjunctivitis sicca (dry eyes), and optic neuritis, which may rapidly lead to loss of vision. Heerfordt syndrome includes fever, parotid gland enlargement, facial palsy, and anterior uveitis.1
Hepatic involvement is common at disease onset but usually does not cause signs or symptoms.54 Although histologic evidence of hepatic sarcoidosis is present in more than one-half of sarcoidosis patients,55 signs of organ dysfunction due to hepatic sarcoidosis are far less common.54 Hepatomegaly, abdominal pain, and pruritus are present in only 15%–25% of patients with hepatic sarcoidosis. An increased serum alkaline phosphatase level occurs in approximately one-third of patients,56 but it is rarely associated with permanent hepatic dysfunction and therefore does not mandate treatment.54,56 Treatment is required in the rare patient with significant symptoms, evidence of synthetic dysfunction, or hyperbilirubinemia. Rarely, hepatic sarcoidosis may lead to a primary biliary cirrhosis-type picture, and portal hypertension may develop.57
Clinical evidence of cardiac involvement is found in only 5% of sarcoidosis patients,58 although myocardial granulomas have been found in approximately 25% of patients at autopsy.59 Most clinical problems are related to cardiac arrhythmias or left ventricular dysfunction.60,61 Sudden death may occur. Congestive heart failure may result when the myocardium is massively infiltrated with granulomas. Because of the potential lethal nature of heart involvement with sarcoidosis, an electrocardiogram is recommended for every patient diagnosed with the disease.1
Any portion of the central nervous system or peripheral nervous system may be affected by sarcoidosis. Neurosarcoidosis has a predilection for the base of the brain, and cranial neuropathies are the most common manifestation.62 The facial nerve is the cranial nerve most frequently involved.62 In fact, it is common for Bell palsy to be the first manifestation of sarcoidosis and resolve completely before other manifestations of the disease occur. Mass lesions may develop in the brain or spinal cord. Aseptic meningitis and peripheral neuropathy are other neurologic manifestations of sarcoidosis.63
The sinuses and upper airway are commonly involved with sarcoidosis, a condition known as SURT: sarcoidosis of the upper respiratory tract.64 Nasal SURT is often associated with lupus pernio skin lesions (see Fig. 152-9) and may cause epistaxis and severe nasal crusting. Sarcoidosis of the spleen is not rare.65 Sarcoidosis may also cause a disorder in calcium metabolism that results from activated sarcoidal macrophages demonstrating an increase in 1-α hydroxylase activity. This enzyme converts 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D, the active form of the vitamin, an increase of which may result in hypercalcemia, hypercalciuria, and nephrolithiasis.66 Sarcoidosis may be associated with a reduction in any blood cell line. Leukopenia may result from bone marrow involvement or from splenic sequestration. Thrombocytopenia may result from bone marrow involvement, splenic sequestration, or from an idiopathic thrombocytopenic purpura-like syndrome related to the hypergammaglobulinemia often seen in patients with sarcoidosis.67