A 4-year-old boy presents with “multiple bumps” that have been growing on his face (Figure 150-1). The differential diagnosis of these lesions included cutaneous sarcoidosis and granuloma annulare. A punch biopsy was performed and the diagnosis of sarcoidosis was made.
Papular lesions of sarcoidosis on the face of a 4-year-old boy. (Used with permission from Weinberg SW, Prose NS, Kristal L. Color Atlas of Pediatric Dermatology, 4th edition, Figure 15-23, New York, NY: McGraw-Hill, 2008.)
Sarcoidosis is a multisystem granulomatous disease most commonly involving the skin, lungs, lymph nodes, liver, and eyes. There is no clear gender predominance in childhood sarcoidosis.1 Of interest, outside the US sarcoidosis mainly occurs in the predominant race of the country.2 Higher incidences of cases occur in certain parts of the world, including Sweden in Europe and the South Atlantic and Gulf States in the US.3–5
In the pediatric population, sarcoidosis is divided into early and late onset. Early onset involves children in their first four years of life, presenting with a triad of arthritis, rash, and uveitis.4 In this patient population, typical pulmonary disease occurs in about 22 percent of children in this age group.6 Early onset sarcoidosis is seen mostly in Caucasian patients and these patients may have a protracted course with severe morbidity and residual impairments.7,8
Late onset sarcoidosis in children presents as a multisystem disorder, with lung involvement most common.6 Up to 60 percent of children have an abnormal chest x-ray at initial presentation, with the predominant symptom being a mild, dry, chronic cough.6 The eyes are also affected in older children (20 to 30%).3,9 Symptoms include eye redness, blurred vision, photophobia, and ocular pain. Ophthalmic sarcoidosis manifests as uveitis with anterior segment involvement (84% of cases).9 Other complications include optic neuritis, band keratopathy, cataracts, glaucoma, and retinal vasculitis. Other organ systems may be involved including the reticuloendothelial system (enlargement of lymph nodes),1 cutaneous (erythema nodosum),2 musculoskeletal (joint effusions, arthralgias, myositis),2 renal (nephrocalcinosis, abnormal urinalysis),3,10 cardiovascular (arrhythmias, sudden death),11 central nervous system (seizures, cranial neuropathies, diabetes insipidus, growth hormone deficiency),6,12,13 and hepatic (abnormal liver function tests) systems.14
Juvenile early onset sarcoidosis.
Juvenile late onset sarcoidosis.
Juvenile systemic granulomatosis.
Lupus pernio (sarcoidosis of the face that resembles cutaneous lupus).
Rare in pediatric age group; more common in adolescents and young adults.
Male/female ratio = 1.
Two distinct forms of juvenile sarcoidosis—Early onset and late onset.
Presents within the first four years of life.
Triad of arthritis/rash/uveitis.
Predominantly Caucasian patients.
Progressive and debilitating course
Common types are maculopapular, lupus pernio, cutaneous, or subcutaneous nodules, and infiltrative scars.
Erythema nodosum (EN) occurs in 31 percent of patients with sarcoidosis and is the most common associated skin finding (see Chapter 152, Erythema Nodosum).
Etiology and Pathophysiology
Studies reveal that siblings of patients with sarcoidosis exhibit an increased risk of involvement thus implying a genetic component.15
Sarcoidosis is a granulomatous disease with involvement of multiple organ systems with an unknown etiology.
The typical findings in sarcoid lesions are characterized by the presence of circumscribed granulomas of epithelioid cells with little or no caseating necrosis, although fibrinoid necrosis is not uncommon.
Granulomas are usually in the superficial dermis but may involve the thickness of dermis and extend to the subcutaneous tissue. These granulomas are referred to as “naked” because they only have a sparse lymphocytic infiltrate at their margins.
Clinical Forms of Disease
Cutaneous involvement is either specific or nonspecific.
Typical noncaseating granulomas, no evidence of infection, foreign body, or other causes.
May be disfiguring, but almost always nontender and rarely ulcerate.
Papules, plaques or nodules is most common, red-brown or purplish, usually smaller than 1 cm, and found mostly on face, neck, upper back, and limbs (Figure 150-2).
Lupus pernio type sarcoidosis (Figures 150-3 to 150-5) presents as purplish lesions resembling frostbites with shiny skin covering them, typically affecting nose, cheeks, ears, and lips.
Plaque sarcoidosis is typically chronic, occurring over the forehead, extremities, and shoulders, but may heal without scarring.
Nodular cutaneous and subcutaneous plaques that are skin-colored or violaceous without epidermal involvement are typically seen in advanced systemic sarcoidosis.
Areas of old scars that are damaged by trauma, radiation, surgery, or tattoo may also be infiltrated with sarcoid granulomas (Figures 150-6 and 150-7). Lesions may be tender and appear indurated with red or purple discoloration.
Erythema nodosum (EN) lesions usually are not disfiguring, but tender to touch, especially when they occur with fever, polyarthralgias, and sometimes arthritis and acute iritis.
EN appears abruptly with warm, tender, reddish nodules on the lower extremities, most commonly the anterior tibial surfaces, ankles, and knees.
EN nodules are 1 to 5 cm, usually bilateral, and evolve through color stages: first bright red, then purplish, and lastly a bruise-like yellow or green appearance.
EN is seen in the setting of Löfgren syndrome, appearing in conjunction with hilar lymphadenopathy (bilateral most often), and occasionally anterior uveitis and/or polyarthritis.
Ulceration is typically not observed in EN, which heals without scarring.
Early-onset childhood sarcoidosis may present with enchondromatosis.16
Maculopapular sarcoidosis on the leg. (Used with permission from Amor Khachemoune, MD.)
Lupus pernio type sarcoidosis involving the nasal rim. (Used with permission from Richard P. Usatine, MD.)
Lupus pernio type sarcoidosis with violaceous scarred plaques on cheek of a child. (Used with permission from Kane K, Lio PA, Stratigos AJ, Johnson RA. Color Atlas & Synopsis of Pediatric Dermatology, 2nd edition, Figure 15-18, New York, NY: McGraw-Hill, 2009.)
Lupus pernio (sarcoidosis) with violaceous papules and plaques around the eye and on the cheek of a child. (Used with permission from Weinberg S, Prose NS, Kristal L. Color Atlas of Pediatric Dermatology, 4th edition, Fig. 15-25, McGraw-Hill, 2008.)
Sarcoidal plaque of the knee, which appeared after a trauma to the knee. (Used with permission from Amor Khachemoune, MD.)
Sarcoid on a heart-shaped homemade tattoo over the knee. (Used with permission from Amor Khachemoune, MD.)
Complete blood count (CBC) count with differential:
Serum calcium and 24-hour urine calcium levels:
Hypercalciuria has been found in 49 percent of patients in some studies, whereas 13 percent of patients had hypercalcemia.
Hypercalcemia occurs in sarcoidosis because of increased intestinal absorption of calcium that results from overproduction of a metabolite of vitamin D by pulmonary macrophages.
Serum angiotensin-converting enzyme (ACE) level is elevated:
Chitotriosidase involved in the defense against pathogens containing chitin may be a potential marker for disease activity:
Serum chemistries, such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, blood urea nitrogen (BUN), and creatinine levels. In addition, urinalysis may reveal proteinuria, hematuria, leucocyturia and concentration defect. These levels may be elevated with hepatic and renal involvement.
Other—Elevated erythrocyte sedimentation rate, diabetes insipidus, and renal failure may be noted.
Chest x-ray (CXR):
Intrathoracic lymphadenopathy involving the right paratracheal area and both hila are detected in 95 percent of cases.19
Stage I disease shows bilateral hilar lymphadenopathy (BHL). Stage II disease shows BHL plus pulmonary infiltrates. Stage III disease shows pulmonary infiltrates without BHL. Stage IV disease shows pulmonary fibrosis.
CT of the thorax may demonstrate lymphadenopathy or granulomatous infiltration. Other findings may include small nodules with a bronchovascular and subpleural distribution, thickened interlobular septae, honeycombing, bronchiectasis, and alveolar consolidation.
Pulmonary function tests—Evidence of both restrictive abnormalities and obstructive abnormalities may be found.
Punch biopsy is adequate to obtain a sample of skin that includes dermis.
If EN nodules are deep, a biopsy should also include subcutaneous tissue.
Biopsy specimens are sent for histologic examination, as well as stains and cultures to rule out infectious causes.
Granulomatous plaques of biopsy proven sarcoidosis on the arm of a woman. She also has sarcoidosis of the lung. (Used with permission from Richard P. Usatine, MD.)
Violaceous sarcoidal papules coalescing into annular plaques on the back. (Used with permission from Richard P. Usatine, MD.)
Cutaneous involvement of sarcoidosis is typically not life-threatening and, therefore, the major rationale for treatment is to prevent or minimize disfigurement. Cosmetic issues are particularly important on the face. Also, the lesions can be painful.
Corticosteroids (oral and topical) are the mainstay of treatment.3 SOR B
Steroid sparing agents used to treat sarcoidosis include methotrexate, azathioprine cyclophosphamide and cyclosporin.21,22 SOR C
A multidisciplinary approach is imperative in patients with systemic sarcoidosis.
Patients with eye symptoms should be referred to an ophthalmologist (Figure 150-10).
Patients with lung involvement should be referred to a pulmonologist.
Sarcoidosis may affect the following organ systems: pulmonary, reticuloendothelial, musculoskeletal, renal, cardiovascular, neurologic, hepatic; thus, thorough review of systems and results from laboratory work-up should dictate appropriate referral.
Sarcoidosis of the eye with involvement of the conjunctiva and infiltration of the inner lower eyelid. (Used with permission from Richard P. Usatine, MD.)
As the cause remains to be elucidated, no preventative measures have been established. Patients presenting with cutaneous sarcoidosis should be screened as clinically indicated.
In early onset disease, 80 to 100 percent of patients suffer from chronic debilitating sequelae.7,8
Hilar lymphadenopathy in combination with acute or subacute onset (fever, arthralgia, erythema nodosum) is associated with a remission rate of 80 to 90 percent.23
Hypercalcemia, cutaneous sarcoid lesions, and generalized lymphadenopathy are associated with poorer prognosis.11
Mortality rate has been estimated to be about 1 to 5 percent.24
Patients with cutaneous sarcoidosis should be worked up for systemic sarcoidosis. Regular follow-up is necessary.
Inform patients about the risk that systemic sarcoidosis can occur even if the skin is the only area currently involved.
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