150 AJTCCM VOL. 28 NO. 4 2022
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Background. Sarcoidosis is a multisystem granulomatous condition of uncertain aetiology that most frequently aects the lungs. Because of
clinical and radiological similarities with tuberculosis (TB), particularly in high-prevalence regions, sarcoidosis is frequently misdiagnosed
as TB.
Objective. To review the clinical featuresof sarcoidosispatients in a South African (SA) population, adding clinical information to the
relatively few studies that have been conducted in SA patients with sarcoidosis.
Methods. is was a retrospective study of 102 sarcoidosis patients conducted between 2002 and 2006 at the Charlotte Maxeke Johannesburg
Academic Hospital.
Results. Of 102 sarcoidosis patients, there were 69 (67.6%) females and 33 (32.4%) males. e majority (85.3%) were non-smokers. e
mean age of the group was 44.6years. One-third of patients had chronic comorbid diseases. Almost 17% had been treated initially for TB,
prior to being diagnosed as having sarcoidosis. Two patients developed active TB while receiving corticosteroid treatment for sarcoidosis.
e salient clinical manifestations were dry cough (the most common presenting symptom in 82.4%), dyspnoea in 53.9%, cutaneous lesions
other than erythema nodosum in 33.3%, and on lung examination crackles were noted in 37.3% of patients. Raised angiotensin-converting
enzyme (ACE) levels were found in 56.8% of patients. e majority (48%) of patients had stage II chest radiographic changes. Cutaneous
(28.4%), mediastinal lymph node (25.5%) and transbronchial lung (25.5%) biopsies were the most frequent sites conrming granulomatous
inammation. Overall, 21.2% of patients had obstructive airway disease. Systemic corticosteroids were indicated in 87.3% of patients and
the relapse rate was 60.7%.
Conclusion. Sarcoidosis is oen initially misdiagnosed as TB in SA. e most common biopsy sites for histological conrmation were the
skin and mediastinal lymph nodes, and transbronchial lung biopsies were also frequently taken. Stage II chest radiographic changes were
most common. Overall, systemic corticosteroids were administered in 87.3% of cases and the relapse rate was 60.7%.
Keywords: sarcoidosis, clinical features, tuberculosis
Afr J Thoracic Crit Care Med 2022;28(4):150-156. https://doi.org/10.7196/AJTCCM.2022.v28i4.205
Sarcoidosis is a widespread granulomatous disease of unknown
aetiology, primarily aecting the lungs and the lymphatic system. It
has been reported from almost every corner of the globe, impacting
all races and ethnic groups, with diering epidemiological ndings
from numerous reports. In Europe, the incidence of sarcoidosis
varies from 1 to 64 patients per 100 000 population and in the USA it
is reported as 10-35 per 100 000 persons, more commonly occurring
in the black population.[1] e burden of sarcoidosis in South Africa
(SA) is not clearly known, as accurate epidemiological data are not
available. Initial studies from the beginning of the 1960s indicate
that in SA sarcoidosis was rare. During the late 1960s and 1970s
rates of between 3.7 and 23.2 per 100 000 patients were estimated in
the dierent population groups within SA.[2,3] Geographical regions
and referral bias play important roles in the documented incidence
of sarcoidosis in various studies.[4-6]
While sarcoidosis remains an underdiagnosed disorder, doctors
are alert to it, with growing understanding and increasing awareness.
Owingto its similarities to tuberculosis (TB), sarcoidosis has been
under-reported from developing countries. Furthermore, as the
clinical and radiological features may be similar to those of pulmonary
TB, patients with sarcoidosis are oen initially treated as TB patients.
is study was undertaken with the main objective of studying the
prole of patients with sarcoidosis in Johannesburg, SA. e study
describes and analyses the clinical features of 102 sarcoidosis patients.
Methods
This was a retrospective record review undertaken between 1
January 2002 and 31 December 2006, involving 102 patients seen
at CharlotteMaxeke Johannesburg Academic Hospital (CMJAH)
pulmonology facilities. During this time, the Hillbrow Hospital was
closed owing to reorganisation of medical services in Johannesburg,
with some patients (together with their charts), and some medical
sta, being transferred to CMJAH. e study included the transferred
patients from Hillbrow Hospital and those attending CMJAH. e
diagnosis of sarcoidosis was determined on the basis of compatible
clinical signs, radiological features, together with biopsy evidence
of non-caseating epithelioid granulomas, and by the exclusion of
all established causes of granulomatous inammation as described
in the joint declaration of the American oracic Society (ATS),
the European Respiratory Society (ERS), and the World Association
of Sarcoidosis and Other Granulomatous Disorders (WASOG).[4]
ree patients in the study did not have biopsies performed. ese
Sarcoidosis in Johannesburg, South Africa: A retrospective study
RMorar,1 MB ChB, FCP (SA), MMed (Int Med), PhD ; CFeldman,2 MB BCh, FCP (SA), PhD, DSc
1
Division of Pulmonology, Department of Internal Medicine, Charlotte Maxeke Johannesburg Academic Hospital, and School of Clinical
Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
2 School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
Corresponding author: R Morar (rajenmorar@webmail.co.za)
AJTCCM VOL. 28 NO. 4 2022 151
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patients without histological confirmation
of granulomas were deemed to have
sarcoidosis if they had compatible clinical,
laboratory and radiological features, with an
appropriate response to corticosteroids, and/
or spontaneous resolution, and no evidence
of TB or other cause for their clinical features.
The demographic, clinical, laboratory and
radiographic treatment andoutcome data of
all patients were collected.
Statistical analysis was carried out with
Student’s t-test, the Mann-Whitney U-test for
continuous variables, and the χ2 test, or Fisher’s
exact test (2-tail), for categorical variables, as
appropriate. The GraphPad Prism version
4.0 (GraphPad Soware Inc., USA) was used
to perform the statistical analysis and for
graphic representations of the data. Statistical
signicance was at p<0.05.
e research was approved by the Human
Research Ethics Committee (Medical) of
the University of the Witwatersrand (ref. no.
M110752).
Results
Between January 2002 and December 2006,
102 patients with sarcoidosis were seen by the
pulmonology services at CMJAH. ere were
69 (68%) females and 33 (32%) males. e
mean age (standard deviation (SD)) was 44.6
(12.1)years, ranging from 22 to 77years. e
current cohort did not show the described
classic bimodal age distribution (Fig.1).
Table1 indicates the common comorbid
conditions and the clinical prole reported in
the sarcoidosis patients. Coexisting illnesses
were present in 30% of these patients, most
commonly hypertension, renal dysfunction
(estimated glomerular ltration rate (eGFR)
<90 mL/min/m
2
), obesity and diabetes
mellitus. Most patients were non-smokers
(85.3%). Almost 17% of patients had initially
been treated for TB empirically, without
response, at the local community clinic. Two
patients developed active pulmonary TB while
receiving corticosteroid therapy for sarcoidosis.
ese patients did not receive isoniazid (INH)
prophylaxis. Four (3.9%) patients developed
HIV infection during their follow-up treatment
for sarcoidosis, and their mean CD4 count was
233 cells/µL; 3 patients had CD4 counts <200
cells/µL and 1 patient had a CD4 count of 933
cells/µL. ese patients were referred to the
Infectious Disease HIV Clinic.
The presenting clinical features of the
patients are shown in Table 2. The most
common symptom was cough. Erythema
nodosum occurred in 8 (7.8%) patients and
other non-erythema nodosum cutaneous
manifestations occurred in 27 (26.5%).
Haemoptysis occurred in 2 patients – one
patient had post-TB bronchiectasis and the
other endobronchial sarcoidosis.
Histological conrmation of the diagnosis
was made in 99 (97.1%) patients. The most
common biopsy sites were skin (28.4%),
followed by mediastinal lymph nodes via
mediastinoscopy (25.5%) and transbronchial
lung biopsy via fibreoptic bronchoscopy
(25.5%) (Table3).
Organ manifestations of sarcoidosis were wide
and varied (Table4). oracic manifestations,
including hilar lymphadenopathy and
parenchymal lung involvement, were
present in >70% of the patients. Cutaneous
manifestations included papulonodular rash,
erythema nodosum, disguring facial lesions,
lupus pernio and psoriasis-like rash, which
were conrmed on histological examination.
Ocular manifestations included anterior
uveitis, posterior uveitis, retrobulbar neuritis
and pan-uveitis, which were conrmed by
slit-lamp examination by an ophthalmologist.
Bone and joint manifestations included
reported arthralgias, clinical arthritis and
dactylitis, conrmed as cystic bone lesions
on radiographic examination.
Most patients (n=49; 48%) had stage II chest
radiographic features at the time of diagnosis.
i.e. evidence of hilar and/or mediastinal
lymphadenopathy, together with pulmonary
nodules or reticulonodular inltrates, followed
by stage I in 24 (23.5%) patients. A stage III
chest radiograph was seen in 16 (15.7%)
patients, stage IV in 10 (9.8%) and 3 (2.9%)
had a normal chest radiograph.
e initial laboratory data of the group of
patients showed a mean (SD) Hb of 14.2 (1.83)
g/dL, ranging from 9.0 to 19.1 g/dL; white
cell count 6.90 (3.0) × 109/L, with a range of
1.2-23.5 × 109/L, and platelet count 295 (103)
× 109/L, ranging from 99 to 653 × 109/L. e
erythrocyte sedimentation rate (ESR) was 24
(27) mm/h, with a range of 0-125 mm/h. e
serum angiotensin-converting enzyme (sACE)
concentration was elevated at 116 (307) U/L,
ranging from 9 to 3 000 U/L. The serum
calcium level was 2.39 (0.21) mmol/L; the
liver function test results were: total bilirubin
12 (18) μmol/L, direct bilirubin 4 (12) μmol/L,
alkaline phosphatase (AP) 126 (145) IU/L,
gamma-glutamyl transferase (GGT) 79 (100)
IU/L, alanine transaminase 43 (115) IU/L,
aspartate transaminase 36 (58) IU/L, including
albumin 42 (5) g/dL, and globulin 79 (7) g/
dL – all within the normal range. e serum
electrolytes were: sodium 139 (10) mmol/L,
potassium 4.0 (0.4) mmol/L, chloride 104 (4)
mmol/L, urea 5.3 (2.1) mmol/L and creatinine
91 (32) μmol/L.
Abnormal laboratory data of the patients
are shown in Table 5. Five patients had
anaemia (Hb <11 g/dL), 6 had leukopenia
(white cell count <4 × 109/L) and 2 had
platelets <150 × 109/L. A raised (≥20mm/1st
h) ESR (49 (29)) was found in 36 (40.4%)
20 - 29
Age category, years
Patients, n
40
30
20
10
0
30 - 39 40 - 49
Patients, N Female Male
50 - 59 60 - 69 70 - 79
Fig.1. Age category of patients with sarcoidosis.
152 AJTCCM VOL. 28 NO. 4 2022
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patients. The sACE level was >52 IU in 56.8% of patients and the
serum calcium was elevated (>2.5 mmol/L) in 20 (22.7%) cases.
Hypercalciuria (>300 g/24 h) was observed in 4 (11.1%) of 36
patients in whom it was tested. Raised GGT (>78 IU/L) and AP
(>128 IU/L) were observed in 28 (31.8%) and 19 (21.6%) patients,
respectively. A decreased eGFR (<90 mL/min/m2) was noted in 17
(19.5%) patients.
Table6 indicates the results of pulmonary function tests in patients
with sarcoidosis. Lung function studies were performed on initial
Table1. Common comorbid conditions and clinical prole of
102 patients with sarcoidosis
Comorbid conditions and clinical prole n (%)*
Comorbid diseases
Hypertension 33 (32.4)
Renal dysfunction (eGFR <90 mL/min/m2)
eGFR between 60 and 89
eGFR between 30 and 59
eGFR between 15 and 29
17 (19.5)
8 (7.8)
7 (6.9)
2 (2.0)
Overweight 18 (17.6)
Diabetes mellitus 16 (15.7)
Asthma 12 (11.8)
Gastroesophageal reux disease 12 (11.8)
Clinical prole
Family history of sarcoidosis 3 (2.9)
Non-smokers 87 (85.3)
Smokers (current/ex), n8/7
Previous history of tuberculosis treatment 17 (16.7)
HIV positive, n (%) (mean CD4 count, cells/
µL) 4 (3.9) (233)
eGFR = estimated glomerular ltration rate.
*Except where otherwise indicated.
Table2. Presenting clinical features of 102 patients with
sarcoidosis
Presenting clinical features n (%)
Respiratory
Cough 84 (82.4)
Dyspnoea 54 (53.9)
Chest pain 28 (27.5)
Haemoptysis 2 (2.0)
Crackles 38 (37.3)
Skin
Erythema nodosum 8 (7.8)
Other cutaneous manifestations 27 (26.5)
Ocular 19 (18.6)
Nervous system 3 (2.9)
Constitutional
Weight loss 25 (24.5)
Fever 10 (9.8)
Night sweats 20 (19.6)
Malaise or fatigue 31 (30.4)
Arthralgia 10 (9.8)
Jaundice 1 (1.0)
Asymptomatic 1 (1.0)
Table3. Biopsy sites for histological conrmation in patients
with sarcoidosis
Histological conrmation and biopsy sites n (%)
Histological conrmation 99 (97.1)
Biopsy sites (multiple sites at times)
Skin 29 (28.4)
Mediastinoscopy and lymph node 26 (25.5)
Transbronchial lung biopsy 26 (25.5)
Peripheral lymph node 9 (8.8)
Surgical lung biopsy 8 (7.8)
Clinical 3 (2.9)
Liver 3 (2.9)
Bone marrow and trephine 2 (2.0)
Lacrimal gland 2 (2.0)
Salivary gland 1 (1.0)
Nasal 1 (1.0)
Table4. Organ involvement in patients with sarcoidosis
Organ involvement n (%)
Lung parenchyma 74 (72.5)
Hilar lymphadenopathy 72 (70.6)
Skin 35 (34.3)
Papulonodular rash 20 (19.6)
Erythema nodosum 8 (7.8)
Disguring facial lesions 4 (3.9)
Lupus pernio 2 (2.0)
Psoriasiform rash 1 (1.0)
Peripheral lymphadenopathy 23 (22.5)
Ocular 19 (18.6)
Uveitis (anterior, posterior, pan-uveitis,
retrobulbar) 18 (17.6)
Lacrimal gland enlargement 1 (1.0)
Bone and joints 12 (11.8)
Arthralgia 3 (2.9)
Arthritis 8 (7.8)
Dactylitis 1 (1.0)
Hepatomegaly 10 (10.0)
Splenomegaly 9 (8.8)
Hepatosplenomegaly 7 (6.9)
Cardiac
Dilated cardiomyopathy 3 (2.9)
Cor pulmonale 2 (2.0)
Complete heart block 1 (1.0)
Neurological 3 (2.9)
Aseptic meningitis 2 (2.0)
Cerebrovascular accident 1 (1.0)
Renal stones 2 (2.0)
Parotid enlargement 2 (2.0)
Clubbing 2 (2.0)
Jaundice 1 (1.0)
Asymptomatic 1 (1.0)
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presentation in 99 of the 102 cases. Of the parameters tested, the
forced expiratory volume in 1 second (FEV1) was normal in 56 (56.6%)
patients and the forced vital capacity (FVC) was normal in 73 (73.7%).
e total lung capacity (TLC) was decreased in 12 (15.4%) cases.
Airway obstruction (FEV1/FVC ratio <70) was documented in 21
(21.2%) cases, and a reduced diusion capacity for carbon monoxide
(DLCO) was noted in 29 (37.2%) patients.
e treatments received by the patients are shown in Table7.
Most had an indication for corticosteroids, which were prescribed
in 89 (87.3%) patients. Patients were treated and followed up in
the Respiratory Outpatient Department, together with the other
subspecialties as needed. Duration of follow-up ranged from
3months to >10years. ere was a good initial clinical response
to therapy in most patients, and the few (13; 12.7%) who were
merely observed, as they did not have an indication for therapy,
all had a spontaneous clinical response; however, 54 patients
of the cohort (60.7%) had a relapse, ~2-5years aer initiation
of corticosteroids. Chloroquine was prescribed in 27 (26.5%)
patients, methotrexate (MTX) in 10 (9.8%), azathioprine (AZA)
in 4 (3.9%), colchicine (COL) in 2 (2.0%) and cyclophosphamide
(CYC) in 1 patient. Almost always, MTX, AZA, COL and
CYC were used in addition to steroidssimultaneously and as
steroid-sparing agents, or when patientshad a poor response to
corticosteroid therapy alone. Prophylaxis with INH was not used
and co-trimoxazolewasadministered if patients were receiving
≥2 immunosuppressive agents.Nasal steroids were used to treat
associated chronic rhinitis.
e main indications (sometimes multiple) for corticosteroid
therapy in the 89 patients were their respiratory symptoms (90%)
or their chest radiographic features and/or pulmonary function
test abnormalities. In 13 (14.6%) patients, posterior uveitis or
pan-uveitis was the indication for therapy. e other indications
include disguring facial lesions (n=4; 4.5%) and lupus pernio (n=2;
2.2%), generalised lymphadenopathy (n=4; 4.5%), cardiac disease
(3with dilated cardiomyopathy and 1 with complete heart block),
hepatosplenomegaly and generalised lymphadenopathy (n=3; 3.4%)
and constitutional symptoms (n=3; 3.4%). Hypercalcaemia, renal
calculi and meningitis were indications for steroids in 2 patients
(2.2%) each. ere was 1 (1.1%) patient each with an indication
of jaundice, splenomegaly and neutropenia, parotidomegaly,
superior vena cava obstruction and dactylitis. When combination
therapy was used, it was almost always as additional therapy to
corticosteroids, as steroid-sparing agents or if there was a poor
response to corticosteroid therapy.
Table5. Abnormal laboratory results of patients with
sarcoidosis
Parameter n (%) Mean (SD)
Anaemia (Hb <11 g/dL) (n=94) 5 (5.3) 10.2 (0.7)
Leukopenia (WCC <4 × 109/L) (n=94) 6 (6.4) 3.1 (0.9)
rombocytopenia (Plt <150 × 109/L)
(n=91) 2 (2.2) 105 (5)
Raised ESR (≥20 mm/1st h) 36 (40.4) 49 (29)
Raised ACE (>52 IU) (n=95) 54 (56.8) 180 (396)
Raised serum Ca++ (>2.50 mmol/L)
(n=88) 20 (22.7) 2.62 (0.19)
Hypercalciuria (>300 g/24 h) (n=36) 4 (11.1) n/a
Raised GGT (>78 IU/L) (n=88) 28 (31.8) 173 (135)
Raised AP (>128 IU/L) (n=88) 19 (21.6) 287 (251)
eGFR <90 (mL/min/m2) (n=87) 17 (19.5) 54 (20)
SD = standard deviation; Hb = haemoglobin; WCC = white cell count; Plt = platelets; ESR =
erythrocyte sedimentation rate; ACE = angiotensin-converting enzyme (normal 8-52 IU);
Ca++ = calcium (normal 2.15-2.50 mmol/L); n/a = not applicable; GGT = gamma-glutamyl
transferase (normal 0-78 IU/L); AP = alkaline phosphatase (normal 0-128 IU/L); eGFR =
estimated glomerular ltration rate.
Table7. Treatments received and relapse rate in patients with
sarcoidosis
Treatments received n (%)
CS 89 (87.3)
CQ 27 (26.5)
MTX 10 (9.8)
AZA 4 (3.9)
COL 2 (2.0)
CYC 1 (1.0)
Combination therapy
CS + CQ 20 (19.6)
CS + MTX 4 (3.9)
CS + CQ + MTX 3 (2.9)
CS + CQ + MTX + AZA 2 (2.0)
CS + CQ + MTX + AZA + CYC 1 (1.0)
CS + CQ + COL 1 (1.0)
CS + COL 1 (1.0)
CS + AZA 1 (1.0)
Other
Inhaled steroids 34 (33.3)
Nasal steroids 15 (14.7)
Relapse rate 54 (60.7)
CS = corticosteroids; CQ = chloroquine; MTX = methotrexate; AZA = azathioprine;
COL = colchicine; CYC = cyclophosphamide.
Table6. Pulmonary function tests in patients with
sarcoidosis
Pulmonary function tests n (%)
FEV1 (n=99)
≥80% predicted 56 (56.6)
<80% predicted 43 (43.4)
FVC (n=99)
≥80% predicted 73 (73.7)
<80% predicted 26 (26.3)
FEV1/FVC (n=99)*
75-82 34 (34.3)
<70 21 (21.2)†
TLC (n=78)
≥80% predicted 66 (84.6)
<80% predicted 12 (15.4)
DLCO (n=78)
<80% predicted 29 (37.2)
FEV1 = forced expiratory volume in 1 second; FVC = forced vital capacity;
TLC = total lung capacity; DLCO = diusion capacity for carbon monoxide.
*75-82 considered normal.
†16 patients had a normal FVC and 5 a reduced FVC.
154 AJTCCM VOL. 28 NO. 4 2022
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Discussion
The clinical characteristics of 102 patients with sarcoidosis
have been described, of whom >97% had a histopathologically
conrmed diagnosis. ere was a female gender predominance, a
high prevalence of comorbidities, an extremely high proportion
of symptomatic disease and a high relapse rate. is study adds to
the knowledge of the demographic, clinical and laboratory features
of sarcoidosis patients on presentation, as well as the treatment of
patients with sarcoidosis in SA.
e current study revealed that the median age of the sarcoidosis
patients was 44.6years and 64% were >40years old. Comparable
observations have been made in other SA studies.[2,3] e ATS, ERS
and WASOG statement expresses that sarcoidosis consistently shows
a predilection for adults <40 old, peaking at 20-29years of age.[7,8]
Scandinavian nations and Japan report a second peak in incidence in
women >50years old.[9] Studies in India have highlighted the older
age of onset of sarcoidosis.[10,11] e diagnostic age was 47years in
males and 54years in females in Italy.[12] In other countries, such
as in Spain, the age gap is not as large (men – 44years v. women –
49years).[13] In an Estonian study the average age for men was 34years
and for women 43years.[14] e claim quoted in the literature that
theonset of sarcoidosis peaks between the ages of 20 and 45years,[4]
is not endorsed by the more recent reports, with peak ages closer to
30-55years.
In this study, there were twice as many females (67.6%), similar
to the previous study from Johannesburg (64.6%),[3] although there
were somewhat fewer females in the Cape Town study.[2] Globally,
it has been reported that there is a slight female preponderance in
sarcoidosis,[4,15] even though a male preponderance has been reported
in Indian studies.[10,11] In a worldwide study,[16] there was no denite
gender predominance. ere are signs that gender plays a part in the
manifestation of the disease. In A Case Control Etiologic Study of
Sarcoidosis (ACCESS),[15] women were more likely to have ocular and
neurological involvement and erythema nodosum, and men were
more likely to be hypercalcaemic.
Almost 17% of the current study patients had been treated for TB
before being diagnosed as having sarcoidosis. Two patients developed
conrmed active TB while being treated with corticosteroids. Four
patients contracted HIV infection while receiving treatment for
sarcoidosis; 3 patients had CD4 counts <200 cells/µL and 1 patient
had a CD4 count >900 cells/µL. Patients with advanced HIV and low
CD4 counts who receive antiretroviral therapy (ART) can develop
sarcoidosis with immune reconstitution.[17]
Sarcoidosis is known to occur more frequently in non-smokers; the
majority (87%) of patients in this study were non-smokers. One of
the strongest negative associations to arise from the ACCESS analysis
was a 35% lower chance of sarcoidosis among smokers than never
smokers,[18] a result that is consistent with earlier reports.[19-22] Smoking
seems to have a protective role in the occurrence of sarcoidosis, while
smoking has no impact on the degree, course or outcome of the
illness.[23] Familial sarcoidosis has been well described[24,25] and in
the current study, familial association was seen in 3 patients.
ere was a high prevalence of comorbidities in this cohort, most
of which are common conditions in the general population and need
to be diagnosed and treated promptly to improve the patients’ overall
quality of life (QoL). Comorbidities aecting QoL are more prevalent
in sarcoidosis patients than in the general population[26-28] and add to
the complexity of their disease and its treatment.[27,28] e occurrence of
new comorbidities, whether linked to corticosteroid use, to sarcoidosis
itself or to other factors, is independently and strongly correlated with
adverse outcomes, including poorer QoL, hospitalisation risk and
financial impacts.[29-31] Therefore, the occurrence of comorbidities
during the disease course should be carefully evaluated, monitored and
managed.
e most common symptom in the current study was dry cough
(82%), followed by dyspnoea on exertion (52%), similar to previous
studies.[7] Overall, 35 (34.3%) patients had cutaneous involvement and
8 patients had erythema nodosum. In patients of northern European
descent with sarcoidosis, erythema nodosum as cutaneous involvement
is more common.[32] e ACCESS study found that the prevalence of
skin involvement (excluding erythema nodosum) was 15.9%, and of
erythema nodosum 8.3%.[15] Lung crackles were noted in 32% of the
study patients, and crackles have been reported in 20% and 50% of
patient cohorts worldwide.[7] Two patients presented with haemoptysis,
in 1 case due to post-TB bronchiectasis and the other patient having
endobronchial sarcoidosis. Other possible mechanisms for haemoptysis
include an associated mycetoma, coexistent cavitating TB or a possible
viral bronchitis. Only 1 patient was asymptomatic and was diagnosed
incidentally. Arthralgias were seen in 9% of patients in the current study.
Joint symptoms have been recorded to occur in 25-39% of patients.
[33,34] Hypercalcaemia was found in 23% and hypercalciuria in 11%
(tested in 36 patients). e ACCESS study[35] found hypercalcaemia in
10-20% of patients and hypercalciuria in 40-62%. Raised creatinine
levels and a decreased eGFR were noted in 17 (19.5%) patients; however,
only 2 had renal calculi. Although the frequency of occurrence of renal
involvement in sarcoidosis remains unclear, clinically signicant renal
involvement occurs occasionally.[36,37]
In the current study, leukopenia was seen in 6%, anaemia in 5% and 2
patients had thrombocytopenia. A raised ESR was noted in 36 (40.4%)
patients. Previously, in the Johannesburg study, the ESR was noted to be
elevated in 89% of patients. In the Cape Town study, 50% of patients had
mild anaemia, 2 had leukopenia and 1 patient had thrombocytopenia.
e ESR was commonly elevated, but rarely >90 mm/1st hour. Practically
any haematological abnormality may be seen in sarcoidosis, including
raised ESR, eosinophilia, leukopenia, anaemia, haemolytic anaemia,
peripheral lymphopenia and thrombocytopenia.
[4,33]
In this study, elevated levels of sACE were observed in 56.8%
of patients. Elevated sACE levels occurred in 30 - 80% of
sarcoidosis patients and may be a surrogate marker of the burden
of granulomas.[38] In a previous SA study from Johannesburg,[3]
elevatedsACElevelswere documented in 77.5% of patients.
In the current study, 1 patient presented with jaundice, and elevated
GGT and AP were seen in 32% and 22%, respectively. Hepatic
involvement in sarcoidosis is common in up to 70% of patients;
however, most patients with liver involvement are asymptomatic.[39,40]
e chest radiograph was abnormal in >97% of patients. Stage
II (48%) was found to be the most common radiographic stage of
sarcoidosis identied in the current study. Signicant variability exists
regarding the chest radiographic ndings in dierent studies. Several
series found that stage I was the most common radiographic stage, but
in most reports from Scandinavia, radiographic stages I and II were
recorded to be predominant.[41] e classic sarcoidosis radiographic
AJTCCM VOL. 28 NO. 4 2022 155
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nding is bilateral hilar lymphadenopathy and is believed to be present
in nearly three-quarters of patients.[42] However, some US and British
Isles studies[43] show a disproportionate incidence of radiographic
stage III and IV disease. Previous SA studies[2,3] report that most of
the abnormalities on chest radiography were stages II and III.
Pulmonary function tests in sarcoidosis showed an obstructive
pattern in 21.2% of patients. is could be due to endobronchial
involvement, large thoracic nodes compressing the airways and the
coexistence of asthma. Other studies reported between 30% and 50%
of patients having airway obstruction.[33,44,45] In this study, impaired
diffusion was noted in 29 (37.2%) patients tested. Typical lung
function anomalies in sarcoidosis include reduced lung volumes and
decreased diusion capacity.[38] DLCO is the most sensitive of the lung
function test parameters.[46]
e most frequent sites conrming granulomatous inammation
in the current study were: the skin (28%), mediastinal lymph nodes
(26%) and in transbronchial lung biopsies (26%), with the latter being
performed if no other simpler available site for biopsy was accessible.
A transbronchial lung biopsy diagnostic yield varies from 40% to
>90%, depending on the clinician’s experience.[47]
In the current study, a biopsy was not performed in 3 (2.9%)
patients with highly suggestive clinical, radiographic and laboratory
features and response to corticosteroid therapy. ese features may
be diagnostic, particularly for sarcoidosis stage I (98% reliability)
and stage II (89%).[48] Winterbauer et al.,[49] in an asymptomatic
individual, observed that the presence of bilateral hilar and right
paratracheal lymphadenopathy on chest radiography was specic for
sarcoidosis. is approach has proven to be correct in >95% of cases
of asymptomatic individuals and remains cost-eective, particularly
in developing countries with limited resources.[50]
In the current study, 87.3% of patients had an indication
for corticosteroid treatment. When uveitis, hypercalcaemia or
constitutional symptoms were the indication for treatment, the
response was invariably good. Forty-five patients were treated
because of a pulmonary abnormality. Some patients with abnormal
pulmonary function did not show objective evidence of improvement,
although some felt better. ose with disguring facial lesions and
lupus pernio also improved, as well as those with a high burden of
disease with generalised lymphadenopathy and hepatosplenomegaly.
e patients with parotidomegaly and dactylitis also responded
favourably to therapy.
e duration of follow-up ranged from 3months to >10years,
and 54 (60.7%) patients of the cohort had a relapse 2-5years aer
initiation of corticosteroids. Relapse is likely when antisarcoidosis
drugs are being tapered or discontinued. Reported sarcoidosis relapse
rates range from 13% to 75%, occurring 1-12months aer treatment
tapering or withdrawal.[51]
Study limitations
e current study has certain limitations that should be addressed
in future research. As the facility in which the study was conducted
is a tertiary care and referral centre and a single-centre site, the
ndings may not be generalisable to other institutions or the broader
population. e data are dated and it is possible that if the study
were to be performed currently, the ndings may not be the same;
however, more current research is planned to involve multiple study
sites. Furthermore, the study population is heavily biased towards
patients with sarcoidosis who have mainly pulmonary manifestations,
and therefore does not necessarily reect the ndings in a general
sarcoidosis population. Lastly, there were insufficient data to
determine possible reason(s) for, and circumstances surrounding the
high relapse rate, which need further investigation.
Conclusion
In countries with a high prevalence of TB, such as SA, sarcoidosis is
oen misdiagnosed as TB, as both diseases may look very similar in
many ways. erefore, patients with bilateral hilar lymphadenopathy
with or without pulmonary infiltrates should be evaluated for
the possibility of sarcoidosis, particularly if there are additional
characteristics that suggest this possibility or if the patients are placed
empirically on TB treatment and do not respond appropriately.
Declaration. None.
Acknowledgements. None.
Author contributions. RM contributed to the conception, design,
execution, data acquisition, analysis and draft of the article; and CF
contributed to the conception, design, substantial revision and critical
review of the article.
Funding. None.
Conicts of interest. None.
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Accepted 27 September 2022.
