Necrotizing sarcoid granulomatosis: a case report and review of progresses in this disease

doi:10.4236/health.2011.38089

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Vol.3, No.8, 534-536 (2011) Health

doi:10.4236/health.2011.38089

Necrotizing sarcoid granulomatosis: A case report and

review of progresses in this disease

Guido Epping1, Carlos A. Schwengle1, Riena P. Aliredjo2, Michiel Wagenaar 1

1Department of Pulmonary Medicine, Medisch Spectrum Twente, Enschede, The Netherlands; [email protected]

2Department of Pathology, Medisch Spectrum Twente, Enschede, The Netherlands.

Received 9 May 2011; revised 27 June 2011; accepted 18 July 2011.

ABSTRACT

We present the case of a young male who vis-

ited the emergency room with progressive dys-

pnea and left sided chest pain. A chest X-ray

was performed which showed a pattern of dif-

fuse nodular and reticular opacities. The diag-

nosis of Necrotizing Sarcoid Granulomatosis

(NSG) was made by histopathological examina-

tion of a lung biopsy specimen and by exclud-

ing other causes of granulomatous disease. He

was treated with corticosteroids. Because of

persistent extrapulmonary (ocular) involvement

a maintenance dose of prednisone was needed.

Necrotizing Sarcoid Granulomatosis is a granu-

lomatous disease with necrosis and vasculitis

of unknown cause. The resemblance between

NSG and (nodular) sarcoidosis is strong, but

subtle differences exist. The prognosis is good

and therapy is usually not necessary. However

in some cases there is a need for therapy with

corticosteroids, depending on the involved or-

gans and/or the degree of impairment.

Keywords: Necrotizing Sarcoid Granulomatosi s;

Sarcoidosis; Extrapulmonary Involvement;

Computed Tomography; Pathology

1. CASE PRESENTATION

A 21 year old non-smoking male was presented at the

emergency department of our hospital. He suffered from

pain in his right shoulder and on the left side of his chest,

with progressive shortness of breath for two days. He

had a productive cough with clear blank sputum. There

was no haemoptysis, nor were there co nstitution al symp-

toms like fever or night sweats. There were no com-

plaints that could be related to a vasculitis-like disease,

e.g. vision problems, joint aches, skin problems or ab-

dominal discomfort. He had a blank history, and didn’t

use any medication.

Our patient was tachypnoeic with an oxygen satura-

tion of 98% with 3 litres of supplemental oxygen per

minute. His blood pressure was 110/70 mmHg with a

regular pulse of 115/minute. He had a low grade fever,

with a temperature of 38,2oC. There were no palpable

lymph nodes. Chest examination revealed wheezing on

both sides and crackles at the bases. There were no other

abnormalities at the physical examination.

The posteroanterior view of the chest X-ray showed

diffuse reticular and nodular opacities of both lungs

(Figure 1). A computed tomography of the chest and

upper abdomen (Figure 2) showed mediastinal and right

hilar lymphadenopathy. Diffusely dispersed alveolar

opacities were present in both lungs, which were more

pronounced in the lower lobes.

Laboratory findings showed an elevated erythrocyte

sedimentation rate. The C-reactive protein and white cell

counts were both minimally elevated. The serum angio-

tensin converting enzyme (ACE) level was low. Anti-

nucleair antibodies (ANA) and anti-neutrophil cytopla-

smatic antibodies (ANCA) were both negative. Analysis

of his urine showed no abnormalities. Pulmonary func-

tion tests showed a restrictive pattern (TLC = 53% of

reference) with a diminished diffusion capacity (DLCO =

48%). Arterial blood gas analysis (ABGA) breathing

room air showed a mild hypoxemia (pO2 9.6 kPa), with

normocapnia ( pC O2 5.1 kPa).

We performed extensive microbiological testing. All

tests on tuberculosis were negative (Mantoux; Quanti-

feron TB Gold test; Acid-fast staining; PCR tests and

cultures). Serological tests on HIV, viral respiratory infe-

ctions (adenovirus; influenza A/B; parainfluenzae 1/2/3/;

RS virus) and so-called atypical pathogens (chlamydia

pneumoniae and psittaci; coxiella burnetii; legionella

pneumophila; mycoplasma pneumonia) were all nega-

tive.

Bronchoscopic examination was performed. No en-

dobronchial abnormalities were noted. Central biopsy

and broncho-alveolar lavage (BAL) showed no signs of

malignancy or (specific) inflammation. Cultures were

G. Epping et al. / Health 3 (2011) 534-536

535

Figure 1. Chest X-ray (PA view) with diffusely dispersed re-

ticular and nodular opacities in both lungs.

Figure 2. Computed tomography of the chest with enlarged

lymph nodes both mediastinal and hilar, and diffusely dis-

persed nodular opacities.

negative. The BAL contained a lymphocytosis and neu-

trophilia, with in the differential: 1% eosinophils (nor-

mal < 1% - 2%), 9% neutrophils (normal < 3%), 58%

macrophages (normal > 80%) and 32% lymphocytes

(normal < 15%). The CD4/CD8 ratio was slightly ele-

vated (3,0) and the CD103/CD4 ratio was decreased

(0,12). The BAL results with lymphocytosis, slightly ele-

vated CD4/CD8 ratio and a diminished CD103/CD4

ratio were compatible with sarcoidosis.

Vasculitis and malignancy were less probable but

could not be excluded. A video-assisted thoracoscopic

(VATS) biopsy was performed of the right lung. Histo-

logical examination showed nodular abnormalities con-

sisting of granulomas with epitheloid cells, Langerhans

type giant cells and necrosis. The granulomas were dis-

persed through the parenchyma and along the bronchi a

reflection of vasculitis of the adj acent blood vessels was

seen (Figure 3). The pathological and clinical diagnosis

therefore was: Necrotizing Sarcoid Granulomatosis.

Because of the extensive pulmonary involvement and

the seriousness of his complain ts we decided to treat our

patient with corticosteroids. We started with a dose of

60 mg of prednisone a day and gradually tapered the

dose till zero, over a period of six months. With this re-

gime complete recovery was achieved, with normaliza-

tion of his chest X-ray. His chest pain was completely

disappeared. However, after seven months he developed

a sicca like syndrome of the eye. He was examined by an

ophthalmologist and an octreotide scan was performed,

the diagnosis of dacryoadenitis was made. Prednisone

was reintroduced in a dose of 30 mg a day. Again the

dose was gradually reduced. This time we were unable

to reduce it below a dose of 10 mg a day, because of a

flare of his pulmonary complaints. With a maintenance

dose of ten milligrams he is free of symptoms for a year

now.

2. CURRENT UNDERSTANDING OF NSG

IN HUMAN HEALTH

NSG is a rare entity which was first described by

Liebow in 1973. [1-3] The incidence of NSG is not

known. NSG is more common in females than males and

most are non-smokers. [4] Few cases are published with

a total of seven publications since the case-series by

Churg and Gupta in 1979. [4] The age of presentation

varies, with distribution of cases between the second and

the sixth decade of life. [2,4].

Figure 3. VATS biopsy specimen: in the center vasculitis sur-

rounded by tissue with multiple granulomas (Hematoxylin-

Eosin stain, magnification X 50).

G. Epping et al. / Health 3 (2011) 534-536

536

3. CONCLUSIONS

NSG was originally characterized by the following

three characteristics [2]: 1) on pathological examination

there was a background of sarcoid-like granulomas, a

prominent and usually granulomatous vasculitis, and

varying degrees of necrosis, often superimposed on a

mass of confluent granulomas; 2) on chest X-ray, there

were pulmonary nodules but no enlarged hilar lymph

nodes; and 3) a clinically benign course with minimal or

no therapy.

We present a patient diagnosed with Necrotizing Sar-

coid Granulomatosis, with extrapulmonary involvement.

We reviewed the available literature and addressed dif-

ferent aspects of this disease. NSG is viewed by some as

a vasculitis with sarcomatoid reaction, while others look

at it as a variant of sarcoidosis. Either way it is a disease

of unknown etiology, with a good prognosis that some-

times requires treatment with corticosteroids.

There are histological resemblances between NSG and

sarcoidosis but also with vascu litis. The question wheth-

er NSG is a vasculitis with sarcoid reaction (angiocentric

granulomatosis) or a variant of sarcoidosis, still remains

unanswered. [5] Some believe it is a variant of nodular

sarcoidosis e.g. nodular sarcoidosis with necrosis. [3,6]

Others suggested that some cases of NSG are actually

inactive granulomatous infections. [7] The etiology and

pathogenesis of NSG is still unknown . [4]

REFERENCES

[1] Liebow, A.A. (1973) The J. burns amberson lecture.

Pulmonary angiitis and granulomatosis. American Re-

view of Respiratory Disease, 108, 1-18.

[2] Churg, A., Carrington, C.B. and Gupta, R. (1979) Ne-

crotizing sarcoid granulomatosis. Chest, 76, 406-413.

doi:10.1378/chest.76.4.406

NSG usually involves the lungs, but as in our case ex-

tra-pulmonary involvement has been described. There

are case reports of pleural, eye, skin, liver, spleen, kid-

ney and neurological involvement. [4,8-11]

[3] Churg, A. (1983) Pulmonary angiitis and granulomatosis

revisited. Human Pathology, 14, 868-883.

doi:10.1016/S0046-8177(83)80162-2

[4] Quaden, C., Tillie-Leblond, I., Delobbe, A., et al. (2005)

Necrotising sarcoid granulomatosis: Clinical, functional,

endoscopical and radiographical evaluations. European

Respiratory Journal, 26, 778-785.

doi:10.1183/09031936.05.00024205

The diagnosis of NSG can be suspected based upon

clinical findings, laboratory tests, lung function and ra-

diographic findings (chest x-ray and CT scan). Patients

can present with systemic symptoms, such as fatigue,

fever, night sweats and weight loss. Extra-pulmonary

disease can be symptomatic. Besides, patients can have

respiratory symptoms such as cough, dyspnoea and chest

pain. Physical examination is usually non-specific or

completely normal. Although crackles at lung examina-

tion, joint swelling and splenomegaly can sometimes be

found. All these findings are nonspecific.

[5] Rosen, Y. (2007) Pathology of sarcoidosis. Seminars in

Respiratory and Critical Care Medicine, 28, 36-51.

doi:10.1055/s-2007-970332

[6] Popper, H.H., Klemen, H., Colby, T.V. and Churg, A.

(2003) Necrotizing sarcoid granulomatosis—Is it differ-

ent from nodular sarcoidosis? Pneumologie, 57, 268-271.

doi:10.1055/s-2003-39365

[7] Koss, M.N., Hochholzer, L., Feigin, D.S., Garancis, J.C.

and Ward, P.A. (1980) Necrotizing sarcoid-like granulo-

matosis: clinical, pathologic, and immunopathologic

findings. Human Pathology, 11, 510-519.

Pulmonary function tests are usually normal. [4] La-

boratory findings are non-specific and non-diagnostic.

The erythrocyte sedimentation rate is usually elevated.

ACE is typically low and ANCA is usually negative. [4]

Both sarcoidosis an d vasculitis however, cannot be ruled

out by these laboratory investigations. A chest X-ray or

Computed Tomography of the chest can show alveolar

opacities or infiltrates, a solitary nodule or diffuse nod-

ules, hilar and/or mediastinal lymphadenopathy, pleural

thickening and cavitations. There are no specific radio-

graphic findings that can distinguish NSG from other

granulomatous diseases with certainty. [4]

[8] Alberti, S., Falleni, M., Tarsia, P., et al. (2006) A 13-year-

-old female with shortness of breath and pleuritic chest

pain. European Respiratory Journal, 28, 876-882.

doi:10.1183/09031936.06.00021006

[9] Chittock, D.R., Joseph, M.G., Paterson, N.A.M. and

McFadden, R.G. (1994) Necrotizing sarcoid granuloma-

tosis with pleural involvement: Clinical and radiographic

features. Chest, 106, 672-676.

doi:10.1378/chest.106.3.672

[10] Dykhuizen, R.S., Smith, C.C., Kennedy, M.M., et al.

(1997) Necrotizing sarcoid granulomatosis with ex-

trapulmonary involvement. European Respiratory Jour-

nal, 10, 245-247. doi:10.1183/09031936.97.10010245

To confirm the diagnosis a histological examination of

lung tissue or other involved organs is necessary. A rep-

resentative lung biopsy can be obtained through a VATS

or open lung procedure.

[11] Strickland-Marmol, L.B., Fessler, R.G. and Rojiani, A.M.

(2000) Necrotizing sarcoid granulomatosis mimicking an

intracranial neoplasm: Clinicopathologic features and re-

view of the literature. Modern Pathology, 13, 909-913.

doi:10.1038/modpathol.3880162

Prognosis is generally good with more than 80%

complete recovery, either spontaneous or with therapy.

[2,12] There are no guidelines for the treatment of NSG.

Depending upon disease progression and the degree of

impairme nt, cort i cost eroids should be consid ered .

[12] Lynch III, J.P., Kazerooni, E.A. and Gay, S.E. (1997)

Pulmonary sarcoidosis. Clinics In Chest Medicine, 18,

755-785. doi:10.1016/S0272-5231(05)70417-2