VisualDx - Diagnosis Details - Fever and Rash: Sarcoidosis

Last Updated: 02/19/2010

135 – Sarcoidosis

Sarcoidosis is a granulomatous multisystem disease of uncertain etiology. Approximately one-third of patients with sarcoidosis complain of mild fever (which can last for months), fatigue, and weight loss. Constitutional symptoms appear to happen more frequently in Asians and blacks. Respiratory symptoms include a dry cough, dyspnea, chest pain, and tightness of the chest. Uveitis of the eye can present with photophobia, redness of the eye, and cloudy vision. Lymphadenopathy has a predilection for the axillary, cervical, epitrochlear, and inguinal locations. Splenomegaly is sometimes detectable. Salivary and lacrimal glands can be enlarged, and involvement of the heart, gastrointestinal tract, and upper respiratory tract may occur.

Look For

There is a wide range of cutaneous findings. Violaceous, firm papules at the distal nose (known as lupus pernio), and similar lesions can affect the ears, lips, and face. Firm, smaller papules can be scattered on the cheeks. Larger plaques, of violaceous color, can appear on the face, extremities, buttocks, and back. These plaques can have a peripheral elevation and a central hypopigmentation. Pre-existing scars are common sites for cutaneous lesions to form. Erythema nodosum involving the lower extremities is also seen. Ichthyosis vulgaris-like lesions have been reported.

Diagnostic Pearls

Check for enlarged lacrimal glands by everting the upper eyelid.
Lesions can have significant atrophy in addition to infiltration.

Differential Diagnosis & Pitfalls

Sarcoidosis is a diagnosis of exclusion, on a clinical and histological level. Clinically, sarcoid papules, nodules, and plaques are not unique, and a histologic evaluation is often required. The histological differential is broad, and detailed histological findings are beyond the scope of this text. Special stains for acid-fast and fungal organisms and tissue cultures should be obtained when necessary.
The following is a clinical differential.

Papules:
Acne rosacea
Granuloma annulare – Biopsy will assist in differentiation.
Leprosy – Skin lesions are anesthetic. Look for inflamed nerve and acid-fast bacilli on skin biopsy.
Tuberculosis –Tuberculin skin testing (Mantoux test); submit sputum for smear and culture of acid-fast bacilli.
Lichen planus – Violaceous, flat-topped papules that are pruritic. Biopsy will differentiate.
Trichoepitheliomas
Tuberous sclerosis (Adenoma sebaceum)
Lupus erythematosus – Check ANA, anti-ds DNA.
Secondary syphilis – Check RPR, fluorescent treponemal antibody (FTA), look for systemic symptoms, history of primary chancre.

Nodules:
Leukemia cutis / lymphoma cutis
Pseudolymphoma
Tertiary syphilis – Check RPR, FTA, look for systemic symptoms, history of primary chancre.

Plaques:
Tuberculosis – Tuberculin skin testing (Mantoux test); submit sputum for smear and culture of acid-fast bacilli.
Necrobiosis lipoidica
Psoriasis – Pruritic, characteristic silvery, scaly plaques.
Tinea corporis – Check KOH.
Morphea – Look for shiny, taut appearance. Biopsy will assist in differentiation.
Ichthyosis
Leprosy – Lesions are anesthetic; look for inflamed nerve and acid-fast bacilli on skin biopsy.
Leishmaniasis (Old World and New World)– Usually develop into plaques with central ulceration. Microscopy or biopsy should reveal the parasite in majority of cases.
Wegener's granulomatosis
Rhinoscleroma

Best Tests

The serum ACE level is elevated in approximately 60% of patients, but there is a high false-positive incidence; therefore, the diagnostic value of this test is limited. There is cutaneous anergy in sarcoidosis, and more than 60% of patients do not respond to the tuberculin test. Chest radiography will reveal bilateral hilar adenopathy with or without pulmonary infiltrates. A pulmonary function test will show decreased vital capacity, residual volume, and total lung capacity. Lesional skin biopsy reveals well-defined oval or round granulomas with limited numbers of lymphocytes at the periphery of the lesion.

Management Pearls

Even limited lesions of sarcoidosis warrant a systemic evaluation with radiography and blood tests. Cutaneous lesions respond to systemic corticosteroid therapy; however, in the absence of other systemic involvement, this long-term therapy is difficult to justify.

Therapy

Corticosteroids are widely used to control the systemic and cutaneous symptoms of sarcoidosis. Topical clobetasol propionate twice daily to involved areas circumvents the need for systemic corticosteroids. Chloroquine (250 mg/day) and hydroxychloroquine (200 mg/day or twice daily) are sometimes helpful. Methotrexate and other immunosuppressives are used with varying degrees of success.

References

Costabel U, Ohshimo S, Guzman J. Diagnosis of sarcoidosis. Curr Opin Pulm Med. 2008 Sep;14(5):455-61. PubMed Id: 18664976

Rose AS, Tielker MA, Knox KS. Hepatic, ocular, and cutaneous sarcoidosis. Clin Chest Med. 2008 Sep;29(3):509-24, ix. PubMed Id: 18539241

Asukata Y, Ishihara M, Hasumi Y, Nakamura S, Hayashi K, Ohno S, Mizuki N. Guidelines for the diagnosis of ocular sarcoidosis. Ocul Immunol Inflamm. 2008 May-Jun;16(3):77-81. PubMed Id: 18569792

Doherty CB, Rosen T. Evidence-based therapy for cutaneous sarcoidosis. Drugs. 2008;68(10):1361-83. PubMed Id: 18578557

Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med. 2007 Nov 22;357(21):2153-65. PubMed Id: 18032765

Margolis R, Lowder CY. Sarcoidosis. Curr Opin Ophthalmol. 2007 Nov;18(6):470-5. PubMed Id: 18162998

Baughman RP, Lower EE. Evidence-based therapy for cutaneous sarcoidosis. Clin Dermatol. 2007 May-Jun;25(3):334-40. PubMed Id: 17560311

Fernandez-Faith E, McDonnell J. Cutaneous sarcoidosis: differential diagnosis. Clin Dermatol. 2007 May-Jun;25(3):276-87. PubMed Id: 17560305

Marchell RM, Judson MA. Chronic cutaneous lesions of sarcoidosis. Clin Dermatol. 2007 May-Jun;25(3):295-302. PubMed Id: 17560307

Badgwell C, Rosen T. Cutaneous sarcoidosis therapy updated. J Am Acad Dermatol. 2007 Jan;56(1):69-83. PubMed Id: 17190623

Tchernev G. Cutaneous sarcoidosis: the "great imitator": etiopathogenesis, morphology, differential diagnosis, and clinical management. Am J Clin Dermatol. 2006;7(6):375-82. PubMed Id: 17173472

Bonfioli AA, Orefice F. Sarcoidosis. Semin Ophthalmol. 2005 Jul-Sep;20(3):177-82. PubMed Id: 16282152

Heffernan MP, Anadkat MJ. Recalcitrant cutaneous sarcoidosis responding to infliximab. Arch Dermatol. 2005 Jul;141(7):910-1. PubMed Id: 16027318

Associated Findings

Appearance
No Acute Distress
Patient Appears Ill

Body Location
Cheek
Ear
Eyelids
Face
Gingival-Alveolar Mucosa
Inferior Eyelid
Nose
Occipital Scalp
Posterior Neck
Scalp
Superior Eyelid

Configuration
Annular
Arcuate
Linear

Distribution
Bilateral
Scattered Few
Scattered Haphazard
Upper Lobes

Laboratory
ACE Elevated
Alkaline Phosphatase Elevated
Bilirubin Elevated
Calcium 24 Hour Urine Elevated
Eosinophilia
Erythrocyte Sedimentation Rate (ESR) Elevated
Hematocrit Decreased (Anemia)
Hypercalcemia
Kveim-Siltzbach Test Positive
Leukopenia
Lymphopenia
Neutropenia
Rheumatoid Factor Positive
Thrombocytopenia
Transaminases Elevated

Lesion
Atrophy
Conjunctival Injection (Redness, Bloodshot Eyes)
Conjunctival Nodule
Conjunctival Papillae
Conjunctival Plaque-Like
Corneal Small Punctate White Spots
Gingival-Alveolar Nodule
Gingival-Alveolar Papule
Hilar Lymphadenopathy
Hypertrophic Scar - Keloid
Ill-Defined Nodules/Masses
Iris Nodules and Spots
Leonine Facies
Mediastinal Lymphadenopathy
Nodular Interstitial Pattern
Nodule
Papule
Plaque
Reticular Interstitial Pattern
Reticulonodular Pattern

Occupations
Military

Signs and Symptoms
Anorexia (Loss of Appetite)
Arthralgia (Joint Pain)
Blurred Vision
Chest Pain
Cough
Cranial Nerve Palsy
Dry Eyes
Dyspnea (Shortness of Breath, SOB)
Fatigue (Lethargy, Weariness)
Fever (Febrile)
Generalized Weakness (Asthenia)
Hepatomegaly
Hoarseness
Lacrimal Gland(s) Enlarged
Lacrimation
Lung Exam - Crackles
Lung Exam - Rhonchi
Lung Exam - Stridor
Lung Exam - Wheezing
Lymphadenopathy
Malaise
Nasal Congestion
No Fever (Afebrile, Apyrexial)
Non-Productive Cough
Ocular Pain (Eye Pain)
Papilledema
Parotid Enlargement
Photophobia
Splenomegaly
Weight Loss

Temporal
Developed Chronically Lasting Months to Years
Developed Steadily Over Weeks to Months

Medical History
Erythema Nodosum
Keratopathy, Band

Authors
Art Papier MD, William Van Stoecker MD