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Sarcoidosis enters into any physicians' differential diagnosis of a systemic illness with no obvious cause. The disease is more common in males and is ten times more frequent in American blacks. The disease may be discovered incidentally on routine chest radiographs as bilateral lung hilar lymphadenopathy. However, any organ can be involved and almost every clinical presentation has been documented depending upon the organs affected. The clinical course is unpredictable but 65-70% may recover with minimal residual changes. Permanent loss of lung function may occur in 20%. About 10% of patients die of cardiac, central nervous system disease, or progressive pulmonary fibrosis. Treatment is usually with steroids.

The histologic hallmark of the disease is the non-caseating granuloma composed of an aggregate of epithelioid histiocytes with Langhans' type giant cells. Rarely necrosis is identified. The lung is the most common site of involvement but as mentioned, any organ may be involved.

An abnormal immune response to a yet unidentified antigen is suspected as the cause. Patients have an increase in CD4+ Helper T lymphocytes and elevated levels of soluble IL-2 receptors. PCR studies have revealed mixed results over the possibility of a mycobacterial cause.


Disease Associations  
Gross Appearance and Clinical Variants  
Histopathological Features and Variants  
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Sarcoidosis presenting in patients older than 50 years.

Lenner R, Schilero GJ, Padilla ML, Teirstein AS.

Department of Pulmonary and Critical Care Medicine, Mount Sinai-NYU Medical Center, New York, NY, USA.

Sarcoidosis Vasc Diffuse Lung Dis 2002 Jun;19(2):143-7 Abstract quote

BACKGROUND: Sarcoidosis occurs most often between 20 and 40 years of age, but also presents in children and older adults. Newly diagnosed sarcoidosis in older patients has received little attention. In order to characterize sarcoidosis in older patients, the clinical, radiographic and laboratory features of sarcoidosis presenting in patients aged 50 or older were compared to patients whose sarcoidosis was diagnosed at an earlier age.

METHODS: The medical records of 181 consecutive patients with sarcoidosis were reviewed. They were divided into 92 patients diagnosed at 50 years of age or older (group A), and 89 whose diagnosis preceded age 50 (group B).

RESULTS: Comparison of group A with group B revealed that the two groups were similar with regard to race, gender, smoking habits, common presenting symptoms, organ system involvement, pulmonary function data, radiographic stage, PPD status, and laboratory values. At the time of diagnosis, most patients in both groups presented with either respiratory symptoms or asymptomatic chest roentgenogram abnormalities. The most prevalent pulmonary function abnormality was reduced diffusing capacity in both groups. Most patients exhibited either stage I or II chest roentgenograms. Organ systems most commonly involved included lung, lymph nodes, and skin.

CONCLUSION: Sarcoidosis presents with similar clinical features whether diagnosed in young adults or in patients over the age of 50. The diagnosis of sarcoidosis should be considered in patients presenting over age 50 with characteristic signs and symptoms including chest radiographic evidence of mediastinal lymphadenopathy.



Endobronchial involvement and airway hyperreactivity in patients with sarcoidosis.

Shorr AF, Torrington KG, Hnatiuk OW.

Pulmonary and Critical Care Medicine Service, Walter Reed Army Medical Center, Washington, DC 20307, USA.

Chest 2001 Sep;120(3):881-6 Abstract quote

STUDY OBJECTIVE: To determine the relationship between airway hyperreactivity (AHR) and endobronchial involvement in patients with sarcoidosis.

DESIGN: Prospective series of consecutive patients.

SETTING: Pulmonary clinic of a military, tertiary-care teaching hospital.

PATIENTS: Patients with newly diagnosed sarcoidosis.

INTERVENTIONS: All patients undergoing bronchoscopy for the diagnosis of sarcoidosis underwent an evaluation that included history, physical examination, chest radiography, and spirometry. Bronchoprovocation testing was done using methacholine. During bronchoscopy, six endobronchial biopsy (EBB) specimens were obtained. In patients with abnormal-appearing airways, four specimens were obtained from abnormal areas and two specimens were obtained from the main carina. In patients with normal-appearing airways, four specimens were obtained from a secondary carina and two specimens were obtained from the main carina. A biopsy specimen was considered positive if it demonstrated nonnecrotizing granulomas with special stains that were negative for fungal and mycobacterial organisms. Only patients with histologic confirmation of sarcoidosis were included in the data analysis.

MEASUREMENTS AND RESULTS: The study cohort included 42 patients (57.1% were men, 61.9% were African American, and mean age [+/- SD] was 37.3 +/- 6.6 years). AHR was present in nine patients (21.4%), while EBB revealed nonnecrotizing granulomas in 57.1% of patients. All patients with AHR had positive EBB findings compared to 45.5% of individuals without AHR (p = 0.005). There was a trend toward lower lung volumes and flow rates in patients with AHR, but this did not reach statistical significance. The mean serum angiotensin-converting enzyme level was higher in patients with AHR (79.3 +/- 53.9 IU/L vs 37.5 +/- 26.7 IU/L, p = 0.05). No other clinical variable correlated with the presence of AHR.

CONCLUSIONS: AHR may be seen in patients with sarcoidosis. Endobronchial involvement significantly increases the risk for AHR and may play a role in the development of AHR in patients with sarcoidosis. Other clinical factors are not clearly associated with AHR in patients with sarcoidosis.


Multisystem sarcoidosis and carcinoma of the uterine cervix: an unusual association.

Alliot C, Barrios M, Desplechain C.

Department of Internal Medicine, General Hospital of Ussel, Ussel.

Int J Gynecol Cancer 2001 Jul-Aug;11(4):323-5 Abstract quote

Sarcoidosis malignancy syndrome is a rare phenomenon which remains controversial. We report here the case of a 46-year-old woman presenting with multisystem sarcoidosis 12 months after the completion of combined treatment for stage III squamous cell carcinoma of the uterine cervix; at the time she was still in complete remission of the tumor. The outcome was rapidly favorable under oral corticosteroid therapy.

The time interval between the two illnesses as well as patient's age strongly suggest a relationship. Possible pathophysiologic mechanisms and the literature regarding uterine tumors are briefly reviewed.


Papular sarcoidosis of the knees: a clue for the diagnosis of erythema nodosum-associated sarcoidosis.

Marcoval J, Moreno A, Mana J.

Department of Dermatology, Pathology, Hospital de Bellvitge, University of Barcelona, Spain.

J Am Acad Dermatol. 2003 Jul;49(1):75-8. Abstract quote

BACKGROUND: In recent years we have systematically explored the skin whenever sarcoidosis was suggested and we have observed with increasing frequency the presence of granulomatous cutaneous lesions of sarcoidosis involving the knees.

OBJECTIVE: We sought to evaluate the specific cutaneous lesions of sarcoidosis involving the knees.

METHODS: A total of 18 patients with biopsy-proven specific cutaneous sarcoidosis predominantly involving the knees were included in the study. Biopsy specimens were evaluated under polarized light.

RESULTS: Of these cases, 4 corresponded to scar-sarcoidosis, 1 to plaque-type sarcoidosis, and 13 were an admixture of papules and minute scars frequently associated with erythema nodosum (papular sarcoidosis of the knees). Foreign particles were observed in 10 of 13 patients with papular sarcoidosis.

CONCLUSION: Papular sarcoidosis of the knees can be considered a frequent form of cutaneous sarcoidosis, mainly observed in acute forms of the disease, and frequently associated with erythema nodosum.


Sarcoidosis initially manifesting as symptomatic hypercalcemia with the absence of organic involvement.

Motoyama K, Inaba M, Emoto M, Morii H, Nishizawa Y.

Department of Metabolism Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine.

Intern Med 2002 Jun;41(6):449-52 Abstract quote

A 53-year-old man was admitted to Osaka City University Hospital on July 21, 1998, for investigation of symptomatic hypercalcemia. Laboratory data on admission revealed that serum Ca had increased to around 12.6 mg/dl and there was a significant increase in urinary Ca excretion. The serum phosphate level remained normal. Although the serum PTH level was below the detection limit, serum 1,25-dihydroxyvitamin D (1,25(OH)2D) was increased.

Diagnosis of sarcoidosis was supported by a negative tuberculin test and by the elevated levels of serum angiotensin-converting enzyme (ACE), lysozyme activity, and CD4/CD8 ratio in bronchoalveolar lavage specimen; there was however no imaging evidence of sarcoidosis such as bilateral hilar lymphnode enlargement on chest X-ray, high resolution CT or 67Ga citrate scintigraphy. Biopsy specimens from the cervical lymphnode revealed no epitheloid cell granulomas or giant cells. Administration of prednisolone achieved a decrease in serum ACE and 1,25(OH)2D levels, followed by restoration of serum Ca and urinary Ca excretion to the normal range, and finally by an increase of serum PTH to the normal level. These observations suggested that the hypercalcemia could be explained by extrarenal production of 1,25(OH)2D.

We report here on this rare case of sarcoidosis with initial symptoms of symptomatic hypercalcemia resulting from extrarenal production of 1,25(OH)2D.

Pulmonary sarcoidosis induced by interferon-alpha therapy.

Butnor KJ.

Department of Pathology, University of Vermont, Burlington, VT, USA.
Am J Surg Pathol. 2005 Jul;29(7):976-9. Abstract quote  

Recombinant interferon-alpha (IFN-alpha) is being increasingly used in the treatment of chronic hepatitis C.

It has been recently recognized that IFN-alpha can induce the development of sarcoidosis, presumably through its ability to stimulate the TH1 immune response. IFN-associated sarcoidosis is histologically similar to de novo sarcoidosis and is characterized by tightly compact epithelioid non-necrotizing granulomas. IFN-induced sarcoidosis may be unsuspected clinically, as the most common side effects of IFN-alpha simulate the symptoms of sarcoidosis.

It is therefore important for pathologists to be aware of this association and encourage clinicians to carefully review the medication history in cases of pulmonary non-necrotizing granulomatous inflammation where there is a history of hepatitis C, as discontinuation of IFN-alpha can ameliorate the symptoms of sarcoidosis.


Where does the antigen of cutaneous sarcoidosis come from?

Kurata A, Terado Y, Izumi M, Fujioka Y, Franke FE.

Department of Pathology, Kyorin University School of Medicine, Tokyo, Japan.

J Cutan Pathol. 2010 Feb;37(2):211-21. Epub 2009 Jul 13. Abstract quote

BACKGROUND: The antigen pathway of cutaneous sarcoidosis remains obscure. We have investigated topographic involvement of inflammatory cells and lymphatic vessels.

METHODS: Eleven cutaneous biopsies from eight patients were studied, along with controls from other granulomatous disorders and various skin lesions. Markers for lymphocytes, dendritic cells (DCs), and lymphatic vessel endothelial cells were detected using immunohistochemistry.

RESULTS: S100(+) and CD1a(+) immature DCs (Langerhans cells) occurred more frequently within the epidermis, whereas S100(+), fascin(+), or CD83(+) maturing DCs occurred more frequently beneath the epithelium in cutaneous sarcoidosis cases than in controls (e.g. CD83, cutaneous sarcoidosis vs. other granulomatous disorders: r = 0.557, p = 0.011). Fascin(+) and CD83(+) mature DCs were often closely attached to CD3(+) T-lymphocytes around dermal granulomas. D2-40(+) lymphatic vessels were often found surrounding dermal granulomas, especially those located in the deeper dermis, in contrast to fascin(+) blood vessels.

CONCLUSIONS: Antigen-capturing by immature DCs seems to take place initially in the epidermis, followed by maturation of DCs. These mature DCs may present the processed antigen to T-lymphocytes that cause dermal granulomas either in the interstitium of the upper dermis, or in or around lymphatic vessels of the lower dermis. Environmental antigen could be verified by skin test.


HLA and sarcoidosis: new pathogenetic insights.

Martinetti M, Luisetti M, Cuccia M.

Servizio di Immunoematologia e Transfusione e Centro di Immunologia dei Trapianti, IRCCS Policlinico S. Matteo, Pavia, Italy.

Sarcoidosis Vasc Diffuse Lung Dis 2002 Jun;19(2):83-95 Abstract quote

Many theories have been presented to account for the immunological and epidemiological features of sarcoidosis; several lines of study support the prevailing opinion that an environmental agent, possibly microbial in origin, may cause sarcoidosis in a genetically predisposed host.

Many polymorphic genes have been suggested to contribute to this genetic susceptibility: genes encoding angiotensin converting enzyme, vitamin D receptor, and interleukin-1, T-cell receptor genes, Gm and Km immunoglobulin genes and, most relevant, HLA genes (classical and non classical). There is also some evidence of an HLA-associated protection against sarcoidosis. The main action of disease-associated HLA molecules is to present specific antigenic peptides in such a way that the recognizing T-lymphocytes initiate an inflammatory response with peculiar pathological consequences.

Other, so-called, non-classical HLA genes coding for proteins involved in antigen processing and presentation, namely TAP, LMP and DM, seem to contribute. Particular alleles of the tumor necrosis factor gene cluster (TNFA, LTA, LTB) are known to be associated with peculiar clinical forms of sarcoidosis. For instance, Lofgren's syndrome, which is an acute form of pulmonary sarcoidosis with frequent spontaneous remission, is marked by the TNFA*2, HLA-DR3 haplotype. How many HLA genes are involved is still unknown, but it is now clear that the HLA region is strongly implicated in the development of sarcoidosis.

Probably, the future lies in isolating and sequencing the putative peptide bound to susceptible MHC molecules which, activating reactive T-cells, is responsible for disease initiation and/or exacerbation. However, the investigative approach should not be confined only to genomic sequences: the temporal and spatial expression of gene products, the post-transcriptional modification of the protein products will be fundamental in determining the basic functional context of developing sarcoidosis.


Detection of HTLV-I proviral DNA in sarcoidosis.

Yajima A, Kawada A, Aragane Y, Tezuka T.

Department of Dermatology, Kinki University School of Medicine, Osaka, Japan. .

Dermatology 2001;203(1):53-6 Abstract quote

'Sarcoidosis-lymphoma syndrome' is known as an association of sarcoidosis with malignant lymphoma.

We report a 56-year-old woman with systemic sarcoidosis who was seropositive for antibody against human T cell lymphoma/leukemia virus type I (HTLV-I). This patient showed integration of HTLV-I proviral DNA within cutaneous sarcoid nodules, but not in peripheral blood mononuclear cells. Neither atypical lymphocytes nor a T cell receptor beta1 gene rearrangement were observed in peripheral blood mononuclear cells or in cutaneous nodules, indicating that the patient did not have a smouldering type of adult T cell lymphoma/leukemia.

Detection of integration of HTLV-I proviral DNA in cutaneous sarcoid nodules could suggest that the sarcoid nodules might have been generated as a protective response to chronic stimuli of HTLV-I.


Am J Dermatopathol 1993;15:203-207

Immune system's ability to handle particulate foreign matter is altered and presence of extraneous material may serve as the stimulus for granuloma formation


Elevated expression of interleukin-18 in the granulomatous lesions of muscular sarcoidosis.

Fukami T, Miyazaki E, Matsumoto T, Kumamoto T, Tsuda T.

Third Department of Internal Medicine, Oita Medical University, 1-1 Idaigaoka, Oita, 879-5593, Japan I

Clin Immunol 2001 Oct;101(1):12-20 Abstract quote

In an attempt to understand the role of interleukin-18 (IL-18) in the pathogenesis of sarcoidosis, we examined the expression of IL-18 in normal muscle and in muscle biopsies from six patients with muscular sarcoidosis.

Western blot analysis demonstrated that IL-18 was identified only in homogenates of granulomatous muscle tissues, but not in normal muscle tissue homogenates. By immunohistochemistry, strongly IL-18-positive cells were distributed predominantly at the boundary zone of the granulomas. They were recognized as activated macrophages by double staining with anti-CD68. Epithelioid cells showed only faint reactivity. Serum IL-18 levels of patients with sarcoidosis were significantly increased compared to those of healthy volunteers. Unlike protein expression, IL-18 mRNA expression was detected even in normal muscles.

Our results coupled with those of previous investigations demonstrating activity of IL-18 in inducing interferon-gamma production suggest a significant role of IL-18 in the pathogenesis of sarcoidosis.


Matrix metalloproteinases and their tissue inhibitors in the lesions of cardiac and pulmonary sarcoidosis: an immunohistochemical study.

Gonzalez AA, Segura AM, Horiba K, Qian S, Yu ZX, Stetler-Stevenson W, Willerson JT, McAllister HA Jr, Ferrans VJ.

Pathology Section, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1518, USA.


Hum Pathol 2002 Dec;33(12):1158-64 Abstract quote

The pathogenesis of the tissue damage and fibrosis in sarcoidosis is poorly understood. The matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) must be considered in this regard, because they control the lysis of connective tissue components.

Immunohistochemical studies (peroxidase and dual labeling for confocal microscopy) of reactivity for MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, and the 4 membrane-type-MMPs were made on tissues from patients with cardiac (n = 4) and pulmonary (n = 5) sarcoidosis.

The granulomas were histochemically similar in both organs. The multinucleated giant cells (MGCs) showed moderate reactivity for MMP-1 and MMP-9 and variable reactivity for MMP-2 and MMP-3; in addition, they showed colocalization of MT-1-MMP, which activates MMP-2. The reactivity of epithelioid cells (ECs) was moderate for MMP-2 and mild for other MMPs. Macrophages showed weaker reactivity for MMPs than did MGCs and ECs. All 3 types of cells showed very low reactivity for TIMPs. Staining for type IV collagen showed focal damage to the basement membranes of cardiac myocytes and pulmonary alveoli near the granulomas. The cells in sarcoid granulomas contain an abundance of MMPs and a paucity of TIMPs. The MGCs also contain MT-1-MMP and thus can activate MMP-2 in the granulomas.

The MMPs can cause damage to adjacent cardiac myocytes and pulmonary alveoli, leading to the interstitial fibrosis produced by sarcoidosis.


Mod Pathol 1999;12:854-862
J Cutan Pathol 1999;26:271-278

Mycobacterial RNA as detected by PCR found in granulomas

Absence of Ribosomal RNA of Mycobacterium tuberculosis Complex in Sarcoidosis.

Marcoval J, Benitez MA, Alcaide F, Mana J.

Author Affiliations: Departments of Dermatology, Microbiology, and Internal Medicine, Hospital de Bellvitge, University of Barcelona, Barcelona, Spain
Arch Dermatol. 2005 Jan;141(1):57-9. Abstract quote

OBJECTIVE: To determine whether Mycobacterium tuberculosis ribosomal RNA (rRNA) is present in fresh tissue specimens from patients with sarcoidosis.

DESIGN: A prospective study.

SETTING: A university-based hospital.Patients Thirty-five patients diagnosed as having sarcoidosis at the University Hospital of Bellvitge, Barcelona, Spain, were included in the study. Fresh tissue samples with granulomatous inflammation were prospectively collected between 1997 and 2001 from all patients. For each sample tested, approximately 1 negative control was included.

MAIN OUTCOME MEASURES: Mycobacterium tuberculosis rRNA was detected using an isothermal enzymatic amplification system of target rRNA of M tuberculosis complex via DNA intermediates. Smears for acid-fast staining and mycobacteriological cultures were also obtained.

RESULTS: A total of 78 biopsy specimens (57 skin, 10 lymph node, 3 lacrimal gland, 2 spleen, 2 lung, 2 muscle, 1 bone, and 1 nerve) collected from 74 patients (35 patients with sarcoidosis and 39 control patients) were included in the study. Stains for acid-fast bacilli and mycobacterial cultures were negative for organisms in all cases. Mycobacterium tuberculosis rRNA was not detected in the specimens from any patients with sarcoidosis or in those from control patients whose cultures were negative for organisms. Ribosomal RNA was detected in 6 tissue specimens from patients with cultures that were positive for M tuberculosis and that were processed in parallel to the samples included in the study.

CONCLUSIONS: Although previous studies have reported that mycobacterial antigens may play a role in granuloma formation in some patients with sarcoidosis, our results suggest that M tuberculosis cannot be considered to be the etiologic agent of the disease.

Alveolar macrophages and T cells from sarcoid, but not normal lung, are permissive to adenovirus infection and allow analysis of NF-kappa b-dependent signaling pathways.

Conron M, Bondeson J, Pantelidis P, Beynon HL, Feldmann M, duBois RM, Foxwell BM.

Kennedy Institute of Rheumatology, London, United Kingdom.

Am J Respir Cell Mol Biol 2001 Aug;25(2):141-9 Abstract quote

Adenovirus (Adv)-mediated gene transfer requires efficient infection of target cells. The objective of this study was to establish whether alveolar macrophages (AM) and T cells (AT) from sarcoid patients were permissive to infection with Adv vectors and if this property could be used to investigate cytokine gene regulation.

Sarcoid and normal bronchoalveolar lavage (BAL) specimens infected with Adv vectors expressing either beta-galactosidase or a green fluorescent protein were analyzed for transgene expression by fluorescence-activated cell sorter (FACS) and direct immunofluorescence, respectively. Expression of surface antigens previously associated with Adv infection, the coxsackie/adenovirus receptor (CAR), alpha v beta 3, and alpha v beta 5 integrins, was also assessed using FACS analysis. Sarcoid AM and AT were found to efficiently express Adv transgenes, unlike AM from normal volunteers, peripheral blood monocytes, and peripheral blood T cells. Cells permissive to Adv infection expressed the CAR and alpha v beta 5 integrin (also alpha v beta 3 integrin for AM). The data indicate that the upregulation of Adv receptors and the ability to infect sarcoid AM and AT are related to the inflammatory environment within the lung. Having demonstrated efficient Adv-mediated transgene delivery to sarcoid AM and AT, a construct encoding porcine I kappa B alpha was then used to investigate the requirement for nuclear factor (NF)-kappa B in the regulation of cytokine gene expression in pulmonary sarcoidosis. Overexpression of I kappa B alpha in sarcoid BAL specimens indicated that tumor necrosis factor-alpha and interleukin (IL)-6 production by AM and interferon (IFN)-gamma production by AT is NF-kappa B dependent, whereas IL-4 production by AT is NF-kappa B independent.

This is the first occasion that the requirement for NF-kappa B in IFN-gamma gene expression within primary human T cells has been demonstrated. The results of this study have implications for the future investigation of molecular pathways in inflammatory lung disease.



Role of fluorodeoxyglucose positron emission tomography in the diagnosis of neurosarcoidosis.

Dubey N, Miletich RS, Wasay M, Mechtler LL, Bakshi R.

Dent Neurologic Institute, Buffalo, NY, USA

J Neurol Sci 2002 Dec 15;205(1):77-81 Abstract quote

A 45-year-old man developed seizures and myelopathy. MRI showed bitemporal and cervical spinal cord hyperintense lesions on T2-weighted and FLAIR images that contrast-enhanced. Initial evaluation for sarcoidosis was negative, including serum angiotensin converting enzyme (ACE) and chest X-ray.

Whole body fluorodeoxyglucose positron emission tomography (FDG-PET) revealed multiple hypermetabolic hilar and mediastinal foci and spinal cord hypermetabolism at the site of MRI abnormality. Temporal lobe MRI lesions were hypometabolic. Mediastinal lymph node biopsy was consistent with sarcoidosis. The brain, spinal cord, and chest metabolic abnormalities together with the clinical presentation were interpreted as being most consistent with sarcoidosis.

FDG-PET helped target the site of biopsy that subsequently confirmed the diagnosis histologically. In patients with perplexing neurologic presentations, whole body FDG-PET can help secure a timely and minimally invasive diagnosis of neurosarcoidosis.


CSF-ACE activity in probable CNS neurosarcoidosis.

Tahmoush AJ, Amir MS, Connor WW, Farry JK, Didato S, Ulhoa-Cintra A, Vasas JM, Schwartzman RJ, Israel HL, Patrick H.

Department of Neurology, MCP Hahnemann University, Philadelphia, PA 19102, USA.

Sarcoidosis Vasc Diffuse Lung Dis 2002 Oct;19(3):191-7 Abstract quote

OBJECTIVE: To redefine the utility of CSF-ACE as a selective indicator of probable CNS neurosarcoidosis.

METHODS: The diagnosis of probable CNS neurosarcoidosis required: (a) biopsy evidence of systemic sarcoidosis, (b) cortical, brainstem, and/or spinal cord deficits, (c) enhancing lesions on brain and/or spinal cord MRI, and (d) exclusion of other etiologies which could account for the neurological deficits. Radioassay measurement of CSF-ACE activity was performed in 11 patients who met our criteria for probable CNS neurosarcoidosis and 207 control patients.

RESULTS: The M +/- SD for CSF-ACE activity was significantly higher (p < 0.05) for the 11 probable CNS neurosarcoidosis patients (9.5 +/- 6.9 nmol/mL/min) than for the control patients (2.9 +/- 2.7 nmol/mL/min). The optimal CSF-ACE activity discriminator value was 8 nmol/mL/min. At this value, the sensitivity and specificity of CSF-ACE activity was 55% and 94%, respectively.

CONCLUSIONS: CSF-ACE activity is a useful biochemical marker of probable CNS neurosarcoidosis when brain and/or spinal cord MRI show diffuse enhancing lesions.



Hepatic sarcoidosis. Clinicopathologic features in 100 patients.

Devaney K, Goodman ZD, Epstein MS, Zimmerman HJ, Ishak KG.

Department of Hepatic and Gastrointestinal Pathology, Armed Forces Institute of Pathology, Washington, D.C.

Am J Surg Pathol 1993 Dec;17(12):1272-80 Abstract quote

The patterns of hepatic injury were studied in 100 patients with a diagnosis of sarcoidosis and clinical evidence of liver disease that led to diagnostic liver biopsy.

Granulomas were present in all patients; they occupied from < 1% to > 90% of the total volume of tissue examined and were most often located in the portal/periportal region. In none of the 100 cases were infectious organisms identified by special stains, culture, or serology. In 99% of cases, these granulomas were noncaseating; in one of the 100 cases central caseation was noted. In addition to the granulomas present in all biopsies, three broad categories of histologic change were found: cholestatic (58%), necroinflammatory (41%), and vascular (20%). Among those with cholestasis, 19 patients had bile duct lesions similar to primary biliary cirrhosis, whereas another 13 had a pattern of periductal fibrosis reminiscent of primary sclerosing cholangitis. In 37 patients with chronic cholestasis, a decrease in the number of bile ducts (ductopenia) was noted. Twelve patients had an acute cholangitis suggestive of mechanical obstruction--although no clinical evidence of ductal obstruction was found. Necroinflammatory changes included spotty necrosis suggesting hepatitis of diverse etiologies (including viral infection and drug reaction) and chronic portal inflammation suggestive of chronic active hepatitis. Vascular changes consisted of sinusoidal dilatation (14 cases) and nodular regenerative hyperplasia (9 cases). In 6% of the patients, the only changes in the biopsy were those of granulomatous inflammation; each of these patients had a dominant mass ("sarcoidoma"), which had been biopsied to rule out tumor. Fibrosis was seen in 21% of the biopsies--periportal (13%), bridging (2%), or cirrhosis (6%).

It is clear that sarcoidosis can cause progressive liver disease with a wide array of histologic features that can mimic those of other primary liver diseases.


Micropapular sarcoidosis simulating lichen nitidus.

Okamoto H, Horio T, Izumi T.

Dermatologica 1985;170(5):253-5 Abstract quote

A 28-year-old woman with sarcoidosis had military, skin-colored papules localized on the upper back. The lesions closely simulated lichen nitidus. Histologic examination of the papule demonstrated the naked granuloma encircled by epidermal collarettes in the papillary dermis. Therefore, the microscopic reaction pattern also resembled those of lichen nitidus.

This case is a unique form of micropapular sarcoidosis in respect to the clinical appearance and microscopic changes.


Nerve granulomas and vasculitis in sarcoid peripheral neuropathy: a clinicopathological study of 11 patients.

Said G, Lacroix C, Plante-Bordeneuve V, Le Page L, Pico F, Presles O, Senant J, Remy P, Rondepierre P, Mallecourt J.

Service de Neurologie et Laboratoire Louis Ranvier, Centre Hospitalier Universitaire de Bicetre, Assistance Publique des Hopitaux de Paris, Universite Paris-Sud, France.

Brain 2002 Feb;125(Pt 2):264-75 Abstract quote

Peripheral neuropathy is a rare, yet treatable manifestation of sarcoidosis, a multisystem disorder characterized by the presence of non-caseating granulomas that are seldom found in nerve biopsy specimens.

In order to learn more about the subject, we reviewed our clinical and pathological findings in a series of 11 patients (six men and five women aged 26-83 years) with symptomatic neuropathy associated with characteristic granulomas in nerve biopsy specimens. Only two patients were known to have sarcoidosis before the occurrence of the neuropathy. The neuropathy was focal or multifocal in six patients, including one with a multifocal neuropathy associated with conduction blocks, and one with a multifocal axonal motor deficit. Four patients had a distal symmetrical deficit and one patient had a Guillain-Barre-like syndrome with facial diplegia and respiratory failure. Serum angiotensin-converting enzyme concentration was elevated in only two patients.

Epineurial granulomas and perineuritis were present in all nerve specimens. The inflammatory infiltrates invaded the endoneurium, following connective tissue septae and blood vessels, in five patients. Multinucleated giant cells were found in eight patients and necrotizing vasculitis in seven. Inflammatory lesions were associated with variable, asymmetrical involvement of nerve fascicles and axon loss.

A muscle specimen was sampled during the same procedure in 10 patients. It showed inflammatory infiltrates and granulomas in nine patients and necrotizing vasculitis in two. Immunolabelling showed a mixed inflammatory infiltrate of T cells (predominantly CD4+ cells) and macrophages, in keeping with a delayed hypersensitivity reaction. In addition to nerve involvement, all patients had at least one other tissue or organ affected, including muscle in nine patients, lungs and/or intrathoracic lymph nodes in eight, skin in three, arthritis in two, and peripheral lymph nodes, stomach and eye in one patient each. Most patients improved on corticosteroids. Two patients remain free of symptoms after 7 years. Severe side-effects of long-term treatment with corticosteroids occurred in two patients, leading to death in one.

This study illustrates the wide range of clinical manifestations of sarcoid neuropathy and the frequent association of granulomatous inflammatory infiltrates with necrotizing vasculitis and with silent or symptomatic involvement of other organs.


Sixteen cases of uveitis associated with sarcoidosis.

Bienfait MF, Baarsma GS.

Int Ophthalmol 1986 Dec;9(4):243-6 Abstract quote

In 210 cases of uveitis sixteen were associated with sarcoidosis.

All patients had bilateral involvement and thirteen patients had a panuveitis. Ophthalmic and systemic findings in these patients are described and compared with the literature.

Nine patients were not known to have sarcoidosis previously; seven of these presented with the typical signs for sarcoidosis, such as periphlebitis with 'candle wax' exudates and/or small chorioretinal lesions.



Am J Dermatopathol 2000;22:408-412.

Polarizable foreign bodies were found in the granulomas of 12/50 patients with cutaneous sarcoidosis and all 12 patients had at least one other systemic lesion

Elements identified by energy dispersive X-ray spectroscopy included calcium, phosphorus, silicon, and aluminum

The presence of foreign bodies does not exclude the diagnosis and indeed, may serve as an inciting stimulus for granuloma formation

Clinical spectrum and histological analysis of 32 cases of specific cutaneous sarcoidosis.

Department of Dermatology, Hopsital Universitari Germans Trias i Pujol, Badalona, Spain.


J Cutan Pathol. 2006 Dec;33(12):772-7 Abstract quote

Background: Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology in which skin involvement is frequent.

Objective: To review histological characteristics of biopsies of specific cutaneous lesions of sarcoidosis and their relationship with clinical course.

Patients and methods: Biopsies from 32 patients with specific cutaneous sarcoidosis were reviewed. Histological findings and clinical characteristics of these patients were analysed.

Results: The initial clinical lesions of the patients were ten infiltrated nodule-plaques, eight papules, four maculopapular eruptions, five scar sarcoidosis, four subcutaneous nodules and one lupus pernio. Sarcoidal granulomas were located at dermis in 31 cases (74%) and at subcutaneous fat in 12 (28%) but only four were subcutaneous exclusively. Perivascular or periannexial distribution of granulomas was observed in eight cases (19%) and they had coalescence in 29 samples. The presence of foreign material was demonstrated in 11 cases (26%).

Conclusions: Clinical spectrum of specific lesions of cutaneous sarcoidosis showed a good correlation with granulomas localization in the biopsies. However, traditional classification of specific cutaneous sarcoidosis is often overlapping. On the other hand, foreign bodies and other atypical histological findings were more common than initially expected.

The histologic spectrum of cutaneous sarcoidosis: a study of twenty-eight cases.

Ball NJ, Kho GT, Martinka M.

Departments of Pathology and Medicine (Dermatology), The University of British Columbia, Vancouver General Hospital, Vancouver, British Columbia, and Department of Laboratory Medicine, Royal Jubilee Hospital, Victoria, British Columbia, Canada.

J Cutan Pathol. 2004 Feb;31(2):160-8 Abstract quote.  

BACKGROUND: Naked sarcoidal granulomas (NSGs) are the characteristic histologic finding in sarcoidosis. This descriptive study was designed to identify the frequency of other histologic changes in cutaneous sarcoidosis.

METHODS: The slides from 28 sequential biopsies previously diagnosed as sarcoidosis in patients with known systemic sarcoidosis were reviewed.

RESULTS: Classic NSGs were identified in 25 biopsies (89%). Four biopsies contained tuberculoid granulomas, two with neutrophils suggesting infection (cultures negative). Five biopsies contained interstitial granulomas that resembled granuloma annulare and necrobiosis lipoidica in one case each. Additional histologic findings included birefringent foreign material in 14 biopsies (50%), focal necrosis (43%), elastophagocytosis (39%), linear peri-neural granulomas resembling leprosy (25%), increased dermal mucin (18%) and lichenoid inflammation (14%) [two with plasma cells resembling syphilis (7%)]. In all but three cases, the clinical morphology of the lesions suggested sarcoidosis. Special stains for mycobacteria and fungi were negative.

CONCLUSIONS: The histologic changes in cutaneous sarcoidosis are more diverse than previously recognized. In sarcoidosis, foreign material may be a frequent nidus for cutaneous granuloma formation. Histologic examination without the clinical history could lead to a misdiagnosis of leprosy, syphilis, other infectious granulomas, rosacea, granuloma annulare, necrobiosis lipoidica, and foreign body reaction in selected cases from this series.

Foreign Bodies in Granulomatous Cutaneous Lesions of Patients With Systemic Sarcoidosis

Joaquim Marcoval, etal.

Arch Dermatol. 2001;137:427-430 Abstract quote

To assess the presence of foreign material in the granulomatous cutaneous lesions of patients with systemic sarcoidosis.

Design and Setting
Observational study reevaluating histological specimens at a university referral hospital.

Sixty-five patients diagnosed as having sarcoidosis who developed granulomatous cutaneous involvement.

Main Outcome Measures
To detect the presence of polarizable foreign particles in cutaneous biopsy specimens and to evaluate the association with clinical features of the patients.

Granulomatous cutaneous involvement was demonstrated in 65 (15.3%) of 425 patients with systemic sarcoidosis. In 14 (22%) of the 65 patients, the cutaneous biopsy specimen showed foreign particles in polarized light. The skin lesions corresponded to 3 different clinical patterns: an admixture of papules and infiltration of previously undetected minute scars (n = 6); scar sarcoidosis (n = 4); and subcutaneous nodules (n = 4). The lesions were located most frequently in the extremities, involving the knees in 10 patients.

The presence of polarizable foreign body material in granulomatous cutaneous lesions is not infrequent in patients with systemic sarcoidosis. Inoculation of foreign matter from a previous inapparent minor trauma may induce granuloma formation in individuals with sarcoidosis.


Giant cell lichenoid dermatitis: a possible manifestation of sarcoidosis.

Goldberg LJ, Goldberg N, Abrahams I, Silvers DN, Szaniawski W, Halperin AJ.

Division of Dermatology, Albert Einstein College of Medicine, New York, NY.

J Cutan Pathol 1994 Feb;21(1):47-51 Abstract quote

Giant cell lichenoid dermatitis is a recently described dermatosis thought to be an unusual lichenoid drug eruption. It is characterized by a generalized, pruritic, papulosquamous eruption sparing palms, soles, face and mucous membranes.

Histopathologic findings include areas of epidermal hyperplasia and atrophy with focal vacuolar alteration of the basal layer, exocytosis and cytoid body formation. The dermis contains a band-like, mononuclear cell infiltrate at the dermoepidermal junction with admixed eosinophils, plasma cells and large multinucleate cells. The histologic differential diagnosis includes infectious processes, sarcoidosis, lichen nitidus, lupus erythematosus and lichen planus.

We report 3 patients with giant cell lichenoid dermatitis, one of whom was subsequently diagnosed as having sarcoidosis. Because giant cell lichenoid dermatitis may resemble sarcoidosis both clinically and histologically, and because cutaneous sarcoid is often associated with systemic involvement, the diagnosis of sarcoid should be strongly considered in patients with giant cell lichenoid dermatitis

Development of Sarcoidosis in Cosmetic Tattoos

Diana D. Antonovich, MD; Jeffrey P. Callen, MD


Arch Dermatol. 2005;141:869-872. Abstract quote

Background  The development of granulomatous lesions within tattoos is a well-recognized occurrence in individuals with sarcoidosis. The characteristic histopathological finding of sarcoidosis is the presence of noncaseating granulomas; however, similar histopathogical findings may be seen in foreign body granulomas. Several reports have challenged the assertion that the presence of foreign material within sarcoidal granulomas is incompatible with a diagnosis of sarcoidosis.

Observations  We describe a patient who had multiple linearly arranged papules along her eyebrows and the vermillion border of her upper lip. She had had cosmetic tattooing performed on these areas 3 year prior to presentation. Histopathologic examination revealed sarcoidal granulomas, polarizable foreign material, and pigment granules. Hilar adenopathy was noted on a chest radiograph. After 4 months of treatment with a midpotency topical steroid and doxycycline, she experienced complete clearance of her cutaneous lesions and normalization of chest x-ray film findings.

Conclusions  This case demonstrates a unique adverse result after cosmetic tattooing and highlights the concept that granulomatous histopathologic findings containing foreign material should not be an exclusionary criterion for the diagnosis of sarcoidosis. In this setting, further investigation for the presence of systemic disease is indicated.



Sarcoidal-type allergic contact granuloma: a rare complication of ear piercing.

Casper C, Groth W, Hunzelmann N.

Department of Dermatology, University of Cologne, Germany.

Am J Dermatopathol. 2004 Feb;26(1):59-62 Abstract quote.  

As body piercing is increasingly en vogue, complications are on the rise as well. Biopsies of such lesions can impose special problems to the reviewing dermatopathologist.

We present two patients who developed papulonodular lesions at the sites of ear piercings. Unexpectedly, the findings included prominent sarcoidal granuloma formation with confluent areas of fibrinoid necrosis. An infectious etiology was excluded. However, patch testing revealed contact allergy to palladium, platinum, and nickel. Interestingly, histopathologic examination of the patch test sites also demonstrated granuloma formation. These findings suggest that the lesions represent allergic contact granulomas.

When confronted with this special type of tissue reaction in skin biopsies of piercing sites, the reviewing dermatopathologist should consider the possibility of an allergic reaction. Careful history and thorough diagnostic procedures, including biopsy of the patch test site can establish the diagnosis of contact allergic granuloma.
Immunohistochemical features of cutaneous granulomas in primary immunodeficiency disorders: a comparison with cutaneous sarcoidosis.

Department of Dermatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.


J Cutan Pathol. 2008 May;35(5):467-72. Abstract quote

BACKGROUND: Cutaneous granulomas can occur in patients with a primary immunodeficiency disorder. In some cases, an infectious cause cannot be revealed. The pathogenesis of these granulomas still remains to be elucidated. The aim of this study was to study differences or overlap between these rare granulomas and sarcoidosis-related granulomas.

METHODS: Markers for T-cell subsets (CD3, CD4, CD8 and CD45RO), Langerhans' cells (CD1a), macrophages (CD68), B cells (CD20) and NK cells (CD56) were stained immunohistochemically. The amount of CD4+ and CD8+ cells in the granulomas was counted. Results were compared with the CD4+/CD8+ ratio in peripheral blood.

RESULTS: In the granulomas of two of three patients with a primary immunodeficiency disorder, the cytotoxic T cells (CD8+) outnumbered the T-helper cells (CD4+) with a counted CD4+/CD8+ ratio <<1. In contrast, the granulomas in the cutaneous sarcoidosis patients showed a predominance of CD4+ cells, with CD4+/CD8+ ratios >2.

CONCLUSIONS: A lower CD4+/CD8+ ratio was found in the cutaneous granulomas of patients with a primary immunodeficiency disorder (unclassified combined immunodeficiency, autoimmune lymphoproliferative syndrome and ataxia teleangiectasia) as compared with the patients with cutaneous sarcoidosis. The possible implications of these findings are discussed in this paper.



Early treatment of stage II sarcoidosis improves 5-year pulmonary function.

Pietinalho A, Tukiainen P, Haahtela T, Persson T, Selroos O; Finnish Pulmonary Sarcoidosis Study Group.

Meltola Hospital, Karjaa, Finland.

Chest 2002 Jan;121(1):24-31 Abstract quote

STUDY OBJECTIVE: To evaluate the 5-year prognosis of patients with stage I and stage II newly detected (< 3 months) pulmonary sarcoidosis treated immediately after diagnosis with prednisolone for 3 months followed by inhaled budesonide for 15 months.

DESIGN: Randomized, double-blind, placebo-controlled, parallel-group study for 18 months. Thereafter, open follow-up without treatment.

SETTING: Twenty pulmonary medicine departments in Finland.

PATIENTS: One hundred eighty-nine adult patients, most of them with normal lung function, were randomized to treatment. One hundred forty-nine patients were followed up for 5 years: 79 patients with initial stage I disease and 70 patients with stage II disease.

TREATMENT: Oral prednisolone for 3 months followed by inhaled budesonide for 15 months (800 microg bid), or placebo tablets followed by placebo inhaler therapy. Thereafter, treatment only on an individual basis in the case of clinical deterioration.

MEASUREMENTS: Yearly follow-up visits with chest radiographs, lung function tests (FEV(1), FVC), diffusion capacity of the lung for carbon monoxide (DLCO), serum angiotensin-converting enzyme (SACE), and serum and urinary calcium measurements.

RESULTS: No initial differences were observed in chest radiographic findings between the active-treatment and placebo-treatment groups, either in patients with initial stage I or stage II(-III) disease. However, after the 5-year follow-up, 18 steroid-treated patients (26%) and 30 placebo-treated patients (38%) still had remaining chest radiographic changes. Placebo-treated patients more frequently required treatment with corticosteroids during the 5-year follow-up (p < 0.05). Steroid-treated patients with initial stage II(-III) disease improved more in FVC and DLCO (p < 0.05). No differences in reported adverse events or in SACE, serum calcium, or urinary calcium values were seen.

CONCLUSION: Immediate treatment of pulmonary stage II(-III) sarcoidosis-but not stage I disease-improved the 5-year prognosis with regard to lung function variables.


Long-term follow-up of neurosarcoidosis.

Ferriby D, de Seze J, Stojkovic T, Hachulla E, Wallaert B, Destee A, Hatron PY, Vermersch P.

Department of Neurology, CHRU de Lille, France.

Neurology 2001 Sep 11;57(5):927-9 Abstract quote

The authors evaluated the long-term clinical outcome of neurosarcoidosis and determined predictive factors of disease course. Twenty-seven patients with neurosarcoidosis were followed for at least 5 years from the onset of neurologic symptoms. Patients with CNS involvement during the course of the disease had a higher Modified Oxford Handicap Scale score than those with peripheral nervous system involvement (p < 0.02).

CNS involvement may be a predictive factor for a less favorable disease course. Early and intensive treatment should be considered in such cases.


Characteristics and outcomes of patients with sarcoidosis listed for lung transplantation.

Arcasoy SM, Christie JD, Pochettino A, Rosengard BR, Blumenthal NP, Bavaria JE, Kotloff RM.

Divisions of Pulmonary, Allergy and Critical Care Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, USA.

Chest 2001 Sep;120(3):873-80 Abstract quote

STUDY OBJECTIVES: To characterize the course of patients with advanced sarcoidosis who have been listed for lung transplantation and to identify prognostic factors for death while they are on the waiting list.

DESIGN: Retrospective cohort study.

SETTING: Tertiary-care university hospital.

PATIENTS: Forty-three patients with sarcoidosis who have been listed for lung transplantation at the University of Pennsylvania Medical Center.

METHODS: A multivariable explanatory analysis using a Cox proportional hazards model was performed to determine risk factors that are independently associated with mortality while patients await transplantation.

RESULTS: Twenty-three of the 43 patients (53%) died while awaiting transplantation. The survival rate of listed patients (as determined by the Kaplan-Meier method) was 66% at 1 year, 40% at 2 years, and 31% at 3 years. In a univariate analysis, the following factors were significantly associated with death on the waiting list: PaO(2) < or = 60 mm Hg (relative risk [RR], 3.4; 95% confidence interval [CI], 1.2 to 9.3); mean pulmonary artery pressure > or = 35 mm Hg (RR, 3.2; 95% CI, 1.1 to 9.5); cardiac index < or = 2 L/min/m(2) (RR, 2.8; 95% CI, 1.2 to 6.6), and right atrial pressure (RAP) > or = 15 mm Hg (RR, 7.6; 95% CI, 3.0 to 19.3). Multivariable analysis revealed that RAP > or = 15 mm Hg was the only independent prognostic variable (RR, 5.2; 95% CI, 1.6 to 16.7; p = 0.006). Twelve patients underwent lung transplantation. Survival after transplantation determined by the Kaplan-Meier method was 62% at both 1 and 2 years, and 50% at 3 years.

CONCLUSIONS: Patients with advanced sarcoidosis awaiting lung transplantation have a high mortality rate with a median survival of < 2 years. Mortality is most closely linked to elevated RAP. While earlier referral may diminish the mortality rate of patients on the waiting list for transplantation, further improvements in posttransplantation outcomes will be necessary to ensure that this procedure truly bestows a survival benefit.

Minocycline for cutaneous sarcoidosis

Arch Dermatol. 2001;137:69-73

Twelve patients with cutaneous sarcoidosis were treated with minocycline, 200 mg/d, for a median duration of 12 months

Three patients had extracutaneous lesions at the time of the study
The median follow-up was 26 months
A clinical response was observed in 10 patients, consisting of complete responses in 8 patients and partial responses in 2 patients
A progression of skin lesions was observed in 1 patient, and lesions remained stable in another patient

Adverse effects were minimal, except in 1 patient, who developed hypersensitivity syndrome
A slight hyperpigmentation occurred in 2 patients at the site of previous lesions, which completely disappeared after minocycline use was discontinued
A relapse of skin symptoms occurred after minocycline withdrawal in 3 patients, who further received doxycycline, 200 mg/d, allowing a complete remission of lesions


Successful treatment of cutaneous sarcoidosis using topical photodynamic therapy.

Karrer S, Abels C, Wimmershoff MB, Landthaler M, Szeimies RM.

Department of Dermatology, University of Regensburg, D-93042 Regensburg, Germany.

Arch Dermatol 2002 May;138(5):581-4

Ulcerative sarcoidosis successfully treated with apligraf.

Streit M, Bohlen LM, Braathen LR.

Dermatology, Inselspital, University of Berne, Switzerland.

Dermatology 2001;202(4):367-70 Abstract quote

The case of a 73-year-old female patient is reported with a 25-year-long history of widespread cutaneous sarcoidosis without any known extracutaneous manifestations.

The skin manifestations started with erythematous and plaque-like lesions that had ulcerated on the legs for the last half-year. A relevant venous insufficiency or other etiology of the ulcers could not be found. Histology from lesions of the trunk and from the surroundings of the ulcers revealed the typical noncaseating granulomas. A systemic involvement could not be observed; leukopenia and a slightly elevated angiotensin-converting enzyme level in the serum were found. Topical steroids did not prove successful on the ulcers.

Apligraf, a bilayered skin equivalent, was transplanted twice on the ulcers leading to complete closure within 3 months. A therapy with systemic steroids could thus be avoided.


Treatment of cutaneous sarcoidosis with thalidomide.

Nguyen YT, Dupuy A, Cordoliani F, Vignon-Pennamen MD, Lebbe C, Morel P, Rybojad M.

J Am Acad Dermatol. 2004 Feb;50(2):235-41 Abstract quote.  

BACKGROUND: Although systemic corticosteroids are effective against cutaneous sarcoidosis, alternative therapies are needed.

OBJECTIVE: We sought to assess the efficacy and tolerance of thalidomide for cutaneous sarcoidosis.

METHODS: We performed a retrospective evaluation of thalidomide (100-200 mg/d) in 12 consecutive patients with cutaneous sarcoidosis treated in a university hospital between 2000 and 2002.

RESULTS: Cutaneous lesions regressed within 1 to 5 months, with an average time of 2 to 3 months for 10 patients. In all, 4 patients achieved complete responses, 6 had partial responses, and 2 had no regression. Nasopharyngeal, pulmonary neurologic, and hepatic symptoms were also attenuated. Thalidomide was well tolerated. The main adverse effect was deep vein thrombosis in 1 patient.

CONCLUSION: Thalidomide efficacy and tolerance in patients with cutaneous sarcoidosis merits further evaluation in a controlled trial.

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Commonly Used Terms

Asteroid bodies -Stellate inclusions within giant cells.

Mikulicz's syndrome-Bilateral sarcoidosis of the parotid and minor salivary glands with uveitis.

Schaumann's bodies-Laminated concretions composed of calcium and protein.

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