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Figure 1.
Papules and scars on the knees in patient 1.

Papules and scars on the knees in patient 1.

Figure 2.
Scar sarcoidosis in patient 7.

Scar sarcoidosis in patient 7.

Figure 3.
Subcutaneous nodular lesions in patient 3.

Subcutaneous nodular lesions in patient 3.

Figure 4.
Cutaneous biopsy specimen showing sarcoid granulomas and foreign particles (hematoxylin-eosin, original magnification ×400).

Cutaneous biopsy specimen showing sarcoid granulomas and foreign particles (hematoxylin-eosin, original magnification ×400).

Figure 5.
The microscopic field shown in Figure 4 under polarized light.

The microscopic field shown in Figure 4 under polarized light.

Clinical Data of the Patients*
Clinical Data of the Patients*
1.
Mañá  JMarcoval  JGraells  JSalazar  APeyrí  JPujol  R Cutaneous involvement in sarcoidosis: relationship to systemic disease. Arch Dermatol. 1997;133882- 888Article
2.
Hunninghake  GWCostabel  UAndo  M  et al. for the American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and Other Granulomatous Disorders, ATS/ERS/WASOG statement on sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 1999;16149- 173
3.
Walsh  NMGHanly  JGTremaine  RMurray  S Cutaneous sarcoidosis and foreign bodies. Am J Dermatopathol. 1993;15203- 207Article
4.
Val-Bernal  JFSanchez-Quevedo  MCCorral  JCampos  A Cutaneous sarcoidosis and foreign bodies: an electron probe roentgenographic microanalytic study. Arch Pathol Lab Med. 1995;119471- 474
5.
Callen  JPCallen  JPedJorizzo  JLedGreer  KEedPenneys  NSedPiette  WWedZone  JJed Sarcoidosis. Dermatological Signs of Internal Diseases. Philadelphia, Pa WB Saunders Co1995;293- 300
6.
Veien  NKStahl  DBrodthagen  H Cutaneous sarcoidosis in Caucasians. J Am Acad Dermatol. 1987;16 ((3, pt 1)) 534- 540Article
7.
Winterbauer  RHBelic  NMoores  KD A clinical interpretation of bilateral hilar adenopathy. Ann Intern Med. 1973;7865- 71Article
8.
Carr  PLSinger  DEGoldenheim  P  et al.  Noninvasive testing of asymptomatic bilateral hilar adenopathy. J Gen Intern Med. 1990;5138- 146Article
9.
Mañá  JGomez-Vaquero  CMontero  A  et al.  Löfgren's syndrome revisited: a study of 186 patients. Am J Med. 1999;107240- 245Article
10.
Israel  HLAlbertine  KHPark  CHPatrick  H Whole-body gallium 67 scans: role in the diagnosis of sarcoidosis. Am Rev Respir Dis. 1991;1441182- 1186Article
11.
Sulavik  SBSpencer  RPPalestro  CJ  et al.  Specificity and sensitivity of distinctive chest radiographic and/or 67Ga images in the noninvasive diagnosis of sarcoidosis. Chest. 1993;103403- 409Article
12.
Rorsman  HDahlquist  IJacobson  S  et al.  Tattoo granuloma and uveitis. Lancet. 1969;227- 28Article
13.
Kennedy  C Sarcoidosis presenting in tattoos. Clin Exp Dermatol. 1976;1395- 399Article
14.
Sowden  JMCartwright  PHSmith  AGHiley  CSlater  DN Sarcoidosis presenting with a granulomatous reaction confined to red tattoos. Clin Exp Dermatol. 1992;17446- 448Article
15.
Collins  PEvans  ATGray  WLevison  DA Pulmonary sarcoidosis presenting as a granulomatous tattoo reaction. Br J Dermatol. 1994;130658- 662Article
16.
Papageorgiou  PPHongcharu  WChu  AC Systemic sarcoidosis presenting with multiple tattoo granulomas and extra-tattoo cutaneous granuloma. J Eur Acad Dermatol Venereol. 1999;1251- 53Article
17.
Newman  LSRose  CSMaier  LA Sarcoidosis. N Engl J Med. 1997;3361224- 1234Article
Study
April 2001

Foreign Bodies in Granulomatous Cutaneous Lesions of Patients With Systemic Sarcoidosis

Author Affiliations

From the Departments of Dermatology (Drs Marcoval, Gallego, Fortuño, and Peyrí), Internal Medicine (Dr Mañá), and Pathology (Dr Moreno), Hospital de Bellvitge, University of Barcelona, Barcelona, Spain.

Arch Dermatol. 2001;137(4):427-430. doi:10-1001/pubs.Arch Dermatol.-ISSN-0003-987x-137-4-dst0038
Abstract

Objective  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.

Patients  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.

Results  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.

Conclusions  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.

SARCOIDOSIS is a multisystemic granulomatous disease of unknown etiology that involves mainly the lungs, mediastinal and peripheral lymph nodes, eyes, and skin. The liver, spleen, salivary glands, heart, nervous system, muscles, bones, and other organs may also be involved.1 The diagnosis is well established when clinical and radiological findings are supported by histological evidence of widespread noncaseous granulomas in 1 or more tissues or positive results of a Kveim test.2 Because of its easy accessibility, the skin biopsy is of great value as a less-invasive diagnostic procedure.1

The finding of polarizable foreign matter in cutaneous epithelioid granulomas traditionally permits the exclusion of the diagnosis of sarcoidosis.35 However, some cases have been reported in which foreign particles were present in granulomatous cutaneous lesions in patients with well-demonstrated systemic sarcoidosis.3,4,6 These findings questioned the significance of the presence of foreign bodies in granulomatous skin lesions of patients with sarcoidosis. With these considerations in mind, we reviewed the data in a series of patients with systemic sarcoidosis and granulomatous cutaneous involvement to ascertain the presence of foreign body material in the skin biopsy specimens and to reevaluate the clinical aspects.

PATIENTS AND METHODS

During a 26-year period (1974-1999), 425 patients were diagnosed as having sarcoidosis at the Sarcoid Clinic of the Hospital de Bellvitge, a 1000-bed teaching institution in Barcelona, Spain. The diagnosis of sarcoidosis was made according to the classic criteria: a compatible clinical and radiological picture; histological demonstration of noncaseous granulomas involving 1 or more tissues, with stains and cultures negative for mycobacteria and fungi or positive results of the Kveim test; and exclusion of other granulomatous diseases. In patients whose tissue biopsy specimens did not provide histological confirmation, the diagnosis of sarcoidosis was accepted if the purified protein derivative of tuberculin test results were negative, other diseases were excluded, and the clinical course was consistent with sarcoidosis.79 We also accepted a diagnosis without a biopsy specimen when the intrathoracic gallium citrate Ga 67 uptake showed a lambda pattern (image resembling the Greek letter produced by gallium uptake in the right paratracheal and bilateral hilar lymph nodes), with or without the panda image (image of the face of a panda produced by gallium uptake in the symmetrical lacrimal and parotid glands).911 All patients with systemic sarcoidosis who had cutaneous lesions were evaluated at the Department of Dermatology. Skin biopsies were performed when granulomatous cutaneous involvement was clinically suspected. Those patients with histologically demonstrated granulomatous skin lesions were included in this study. We collected data about the stage of baseline radiograph and extrathoracic sarcoidosis and the history concerning inoculation of exogenous material into the skin from all patients. Cutaneous biopsy specimens with granulomatous involvement were reexamined under polarized light to detect foreign particles. We excluded asteroid bodies, Schaumann bodies, and the small refractive crystals of calcium carbonate usually encountered in sarcoidosis.

RESULTS

Of 425 patients diagnosed as having systemic sarcoidosis, the biopsy specimens in 65 (15.3%) patients showed granulomatous cutaneous involvement. In 15 biopsy specimens obtained from 14 (22%) of the 65 patients, foreign particles were observed under polarized light. Of these 14 patients, there were 13 women and 1 man (mean age, 50.3 years; range, 33-70 years). The chest radiograph stages and extrathoracic involvement in these patients are shown in Table 1. Only patient 3, who formerly took care of a garden, admitted to previous contact with cactus, and vegetal particles were found in her skin lesions. None of the remaining patients had noticed the inoculation of exogenous material into the skin.

We identified 3 types of cutaneous lesions showing foreign particles: (1) an admixture of papules and previously undetected, infiltrated, minute scars located on the knees (n = 5) (Figure 1) or discrete papules on the elbow (n = 1); (2) infiltration of previously known scars (scar sarcoidosis) involving the knees (n = 4) (Figure 2); and (3) subcutaneous nodules involving the forearms (n = 3) (Figure 3) and the face (n = 1). In general, the lesions were located more frequently in the extremities, involving the knees (n = 10), the arms (n = 4), and the face (n = 1).

Histologically, the lesions were noncaseous (sarcoid) granulomas involving the dermis, subcutis, or both, with minor or no lymphocytic component at the periphery. In the majority of cases, foreign material was detected by standard observation as amorphous or crystalloid material or was suspected when a hole in the vicinity of giant cells was detected during tissue processing. The presence of all foreign bodies was confirmed by examining the specimen under polarized light. Figure 4 shows a sarcoid granuloma with foreign particles, and Figure 5 shows the same microscopic field under polarized light.

COMMENT

The presence of foreign particles in granulomatous cutaneous lesions was demonstrated in 14 (22%) of 65 patients with systemic sarcoidosis and skin involvement. The systemic character of the disease was well documented in all patients by the demonstration of intrathoracic and/or extrathoracic disease, in addition to specific (granulomatous) skin involvement. These results agreed with previous reports by Walsh et al3 and Val-Bernal et al4 and corroborated the observation that foreign body granuloma and sarcoidosis are not mutually exclusive.

In our series, we identified 3 different clinical forms of cutaneous sarcoidosis associated with the presence of foreign bodies: papular sarcoidosis of the knees, scar sarcoidosis, and subcutaneous sarcoidosis. Papular sarcoidosis of the knees was the most frequently occurring form in this series, and it was usually associated with acute sarcoidosis, particularly Löfgren syndrome. Clinically, it consisted of minute granulomatous papules grouped over the knees; some of the papules were linearly arranged, and, in some cases, the papules coexisted with infiltrated minute scars not previously noted by the patient. Of the 4 patients with scar sarcoidosis (granulomatous infiltration of previously known scars), we observed an association with Löfgren syndrome in 3 patients. In contrast, subcutaneous nodules were not associated with erythema nodosum but were observed in chronic forms of the disease.

Based on a large series of patients with cutaneous sarcoidosis, Veien et al6 reported that foreign material was sometimes found in old cutaneous scars probably introduced as a consequence of the initial injury. The propensity of cutaneous sarcoidosis to localize in tattoos has also been reported.1216 More infrequently, specific (granulomatous) cutaneous sarcoidosis involved areas of long-term trauma, surgery, venipuncture, vaccination or inoculation, purified protein derivative of tuberculin skin test, and long-standing scarification marks.4 In all these cases, contamination by foreign matter, such as talc and ash, was suspected. In the present series, the granulomatous cutaneous lesions with foreign bodies were located, in most of the cases, on the knees or forearms of middle-aged women. The knees and forearms are easily exposed to trauma, and prior minor injury in these areas may be imperceptible. Consequently, a history of accidental inoculation of foreign particles cannot be elicited in the majority of cases; we were able to obtain this information in only 1 of our patients.

As in previous reports,3,4 our results suggested that the presence of polarizable matter in a cutaneous granuloma does not exclude the diagnosis of sarcoidosis, particularly when systemic features of the disease are present. Moreover, the presence of foreign bodies in 22% of our patients with systemic sarcoidosis and granulomatous skin involvement suggested that it is not a rare event in specific cutaneous lesions of sarcoidosis. This finding may contribute to the understanding of the pathogenesis of the disease. The cause of sarcoidosis remains obscure. It has been hypothesized that the disease occurs when a genetically susceptible host is exposed to a specific environmental antigen(s). In this event, an exaggerated inflammatory response takes place, characterized by large numbers of activated macrophages and T lymphocytes bearing the CD4 helper phenotype, with a pattern of cytokine production consistent with a TH1-type immune response. As a consequence, granulomas develop in the involved organs.2,17 In addition, it has also been hypothesized that sarcoidosis is a disease in which the immune system's capacity to handle particulate foreign matter is altered and that the presence of foreign bodies, which are often not apparent and remain undetected, in the skin and other organs might provide the stimulus necessary for granuloma formation.3 Therefore, the presence of foreign bodies in some tissues may contribute to defining the patterns of organ involvement and the distribution of the lesions in the skin.

In summary, in our results, the presence of polarizable matter in granulomatous cutaneous lesions was not infrequent in patients with systemic sarcoidosis. Accordingly, foreign bodies and sarcoidosis were not mutually exclusive. The clinical pattern of the lesions observed in our patients suggested that previously undetected minor traumas may provide a nidus for granuloma formation in individuals with sarcoidosis.

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Article Information

Accepted for publication October 18, 2000.

Corresponding author and reprints: Joaquim Marcoval, MD, Department of Dermatology, Hospital de Bellvitge, Carrer Feixa Llarga s/n, Hospitalet de Llobregat, 08907 Barcelona, Spain (e-mail: jmarcoval@csub.scs.es).

References
1.
Mañá  JMarcoval  JGraells  JSalazar  APeyrí  JPujol  R Cutaneous involvement in sarcoidosis: relationship to systemic disease. Arch Dermatol. 1997;133882- 888Article
2.
Hunninghake  GWCostabel  UAndo  M  et al. for the American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and Other Granulomatous Disorders, ATS/ERS/WASOG statement on sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 1999;16149- 173
3.
Walsh  NMGHanly  JGTremaine  RMurray  S Cutaneous sarcoidosis and foreign bodies. Am J Dermatopathol. 1993;15203- 207Article
4.
Val-Bernal  JFSanchez-Quevedo  MCCorral  JCampos  A Cutaneous sarcoidosis and foreign bodies: an electron probe roentgenographic microanalytic study. Arch Pathol Lab Med. 1995;119471- 474
5.
Callen  JPCallen  JPedJorizzo  JLedGreer  KEedPenneys  NSedPiette  WWedZone  JJed Sarcoidosis. Dermatological Signs of Internal Diseases. Philadelphia, Pa WB Saunders Co1995;293- 300
6.
Veien  NKStahl  DBrodthagen  H Cutaneous sarcoidosis in Caucasians. J Am Acad Dermatol. 1987;16 ((3, pt 1)) 534- 540Article
7.
Winterbauer  RHBelic  NMoores  KD A clinical interpretation of bilateral hilar adenopathy. Ann Intern Med. 1973;7865- 71Article
8.
Carr  PLSinger  DEGoldenheim  P  et al.  Noninvasive testing of asymptomatic bilateral hilar adenopathy. J Gen Intern Med. 1990;5138- 146Article
9.
Mañá  JGomez-Vaquero  CMontero  A  et al.  Löfgren's syndrome revisited: a study of 186 patients. Am J Med. 1999;107240- 245Article
10.
Israel  HLAlbertine  KHPark  CHPatrick  H Whole-body gallium 67 scans: role in the diagnosis of sarcoidosis. Am Rev Respir Dis. 1991;1441182- 1186Article
11.
Sulavik  SBSpencer  RPPalestro  CJ  et al.  Specificity and sensitivity of distinctive chest radiographic and/or 67Ga images in the noninvasive diagnosis of sarcoidosis. Chest. 1993;103403- 409Article
12.
Rorsman  HDahlquist  IJacobson  S  et al.  Tattoo granuloma and uveitis. Lancet. 1969;227- 28Article
13.
Kennedy  C Sarcoidosis presenting in tattoos. Clin Exp Dermatol. 1976;1395- 399Article
14.
Sowden  JMCartwright  PHSmith  AGHiley  CSlater  DN Sarcoidosis presenting with a granulomatous reaction confined to red tattoos. Clin Exp Dermatol. 1992;17446- 448Article
15.
Collins  PEvans  ATGray  WLevison  DA Pulmonary sarcoidosis presenting as a granulomatous tattoo reaction. Br J Dermatol. 1994;130658- 662Article
16.
Papageorgiou  PPHongcharu  WChu  AC Systemic sarcoidosis presenting with multiple tattoo granulomas and extra-tattoo cutaneous granuloma. J Eur Acad Dermatol Venereol. 1999;1251- 53Article
17.
Newman  LSRose  CSMaier  LA Sarcoidosis. N Engl J Med. 1997;3361224- 1234Article
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