A 13-year-old African American female came to clinic with a few days history of being more tired and sore upper arms. The arms were worse with carrying her backpack, picking up something or if extended over her head. She denied any fevers, chills, weight loss, skin changes, joint pain, myalgias, nausea, emesis, coughs, urinary or bowel changes or eye changes. She denied any recent illnesses or travel. She had a pet dog that had been well. She had a past medical history of dry skin. She had started playing basketball about one week ago for her school team and had started a new volleyball unit in her gym class around the same time. She also was staying up later to finish her homework because of her new basketball schedule. The family history was contributory for a maternal aunt with arthritis and her mother had been diagnosed with sarcoidosis about 6 weeks previously.
The pertinent physical exam showed a healthy female with normal vital signs, weight at the 50% and height at the 90% and trending normally. HEENT was negative. Her skin examination was negative except for a few closed comedomal acne lesions on her cheeks, and some dry skin on her lower extremities, along with some small bruises on her shins and forearms. The bruises were uniform and had no target areas. Her lung, cardiac, abdominal and neurological examinations were normal. A careful examination of her joints found no erythema or edema and all had full range of motion. She was slightly tender with palpation of the muscles. Raising her arms above her head reproduced the mild pain.
The diagnosis of a healthy female with overuse of her muscles and fatigue due to exercise and decreased sleep was made. The pediatrician discussed the diagnosis with the family and offered symptomatic treatment. “I just wanted to make sure she was okay. I didn’t really pay attention to some of my symptoms and I wanted to make sure she was fine,” the mother stated. “I agree with you that it is always better to look into something than not, but as you are learning, sarcoidosis is rare and it is even less common in children and teens, but it does occur,” he replied to the mother. “Because your mother has sarcoidosis, you will need to be aware of symptoms especially in your lungs, skin, eyes and possibly other places throughout your lifetime. If you aren’t sure about it, talk with your doctor and remind them that your mother had sarcoid. I’m not trying to scare you but your mother is right that if something doesn’t seem right then you probably should get it checked out,” he counseled the teen.
Sarcoidosis is rare and is even rarer in the pediatric age group. Sarcoidosis is seen in all ages with an estimated prevalence is 10-40/100,000 in the U.S. population. Pediatric sarcoidosis has an estimated incidence of 0.2/100,000 per year. For the pediatric age range it is more likely from 9-15 years of age. In adults it commonly presents between 20-39 years but bimodal distribution is also reported. Women are more likely to have sarcoidosis than men. African American females have the highest risk, and usually present slightly older, especially in the 4th decade of life. African American women are also more likely to have more significant disease.
The etiology is unknown but felt to be multifactorial with environmental exposures (e.g. non-organic particulates, metals, mold, insecticides) and infectious disease exposures (e.g. Mycobacterium, Hepatitis C) and genetics being implicated. Various HLA alleles, along with various chromosomal abnormalities (3p, 5p, 5q and 6p) have been implicated.
For adolescents their clinical course most closely follows adult forms of the disease process which usually has pulmonary disease, lymphadenopathy and constitutional symptoms such as fatigue, night sweats and weight loss. Treatment is with corticosteroid and other anti-inflammatory agents. For adults, most patients have remission with few or no consequences (overall 6 months, and late-stage pulmonary involvement.
The main hallmark of sarcoidosis is non-caseating epithelioid granulomas. These can be found almost anywhere in the body (e.g. muscle, liver, spleen, lymph nodes, kidney, central nervous system, etc.), but skin and pulmonary granulomas are more common. Skin changes include papules, plaques, and nodules with a yellow, brown, or red hue color are seen. They are more common on the face. Pulmonary lymphadenopathy if present is usually symmetrical and hilar but can be generalized. Hypercalcemia is also seen with sarcoidosis and can be its presentation. A differential diagnosis of hypercalcemia can be found here.
Early onset saroidosis (EOS) is believed to be caused by a NOD2/CARD15 mutation which plays a role in immune function. It is sporadic with onset in infancy with a symmetric, polyarticular, granulomatous arthritis along with scaly rash and uveitis. In a case series of 30 cases of EOS, the mean presentation age was 17.9 ± 15.8 months. All presented with a skin rash (29/30 with 1 case missing information), 96.2% had non-caseating granulomas (25/26 with 4 cases missing information) and 93.8% had fever (15/16 with 14 having missing information). “[S]kin rash with non-caseating granulomas was a key feature for early diagnosis.”
Blau syndrome is a distinct, autosomal-dominant form of the disease that presents with a characteristic triad of granulomatous dermatitis, uveitis and polyarticular synovitis and tenosynovitis. Basically EOS and Blau syndrome have the same clinical presentations but different genetic patterns.
Questions for Further Discussion
1. What is the differential diagnosis of sarcoidosis?
2. What are indications to see an immunologist or rheumatologist?
- Disease: Sarcoidosis
- Age: Teenager
To Learn More
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Lakdawala N, Ferenczi K, Grant-Kels JM. Granulomatous diseases: Kids are not just little people. Clin Dermatol. 2017 Nov – Dec;35(6):555-565.
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa