Introduction: Sjögren’s syndrome (SS) is a chronic autoimmune multisystemic disease. Respiratory manifestations of SS are polymorphic and vary in severity. Among the possible manifestations, organizing pneumonia (OP) is a rare entity. Reversed halo sign (RHS) is an unusual radiological finding classically related to OP but it is also reported in other forms of interstitial pneumonitis (IP).
Case presentation: We report a case of a 65-year-old woman with dyspnoea and persistent-cough of 2-month duration. She presented with RHS as an initial manifestation of IP related to SS. Chest radiography and computer tomography showed multiple well defined lesions with a central ground glass area and peripheral rim of consolidation. No pathological lymph nodes were found. After investigations, the associated diagnosis of SS was confirmed. The patient started steroids (0.5 mg/kg/day) and after 10 weeks of steroid tapering a significant clinical improvement was observed, with radiological resolution of lung lesions. We make some general considerations about differential diagnosis, conditions related to RHS and different patterns of lung involvement in SS. A report of the literature emphasizes this case as an exceptional way of presentation.
Conclusion: To the best of our knowledge this is the second reported OP case associated with SS manifesting as RHS. RSH as an expression of IP related to SS is exceptional, either in the pattern of OP or non-specific IP

A. Zapatero-Gaviria

D. Bernal-Bello

J. Canora-Lebrato

J.A. Rueda-Camino

M.A. Duarte-Millán

S. Martín-Barón

The Egyptian Rheumatologist

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Reversed halo sign as initial manifestation of interstitial pneumonitis associated with Sjögren’s syndrome

AbstractIntroductionSjögren’s syndrome (SS) is a chronic autoimmune multisystemic disease. Respiratory manifestations of SS are polymorphic and vary in severity. Among the possible manifestations, organizing pneumonia (OP) is a rare entity. Reversed halo sign (RHS) is an unusual radiological finding classically related to OP but it is also reported in other forms of interstitial pneumonitis (IP).Case presentationWe report a case of a 65-year-old woman with dyspnoea and persistent-cough of 2-month duration. She presented with RHS as an initial manifestation of IP related to SS. Chest radiography and computer tomography showed multiple well defined lesions with a central ground glass area and peripheral rim of consolidation. No pathological lymph nodes were found. After investigations, the associated diagnosis of SS was confirmed. The patient started steroids (0.5mg/kg/day) and after 10weeks of steroid tapering a significant clinical improvement was observed, with radiological resolution of lung lesions. We make some general considerations about differential diagnosis, conditions related to RHS and different patterns of lung involvement in SS. A report of the literature emphasizes this case as an exceptional way of presentation.ConclusionTo the best of our knowledge this is the second reported OP case associated with SS manifesting as RHS. RSH as an expression of IP related to SS is exceptional, either in the pattern of OP or non-specific IP

Duarte-Millán, M.A.

Bernal-Bello, D.

Rueda-Camino, J.A.

Martín-Barón, S.

Canora-Lebrato, J.

Zapatero-Gaviria, A.

Elsevier - Publisher Connector 

Reversed halo sign as initial manifestation of interstitial pneumonitis associated with Sjögren’s syndrome 

The Egyptian Rheumatologist xxx (2016) xxx–xxxContents lists available at ScienceDirect
The Egyptian Rheumatologist
journal homepage: www.elsevier .com/locate /e j rCase reportsReversed halo sign as initial manifestation of interstitial pneumonitis
associated with Sjögren’s syndromehttp://dx.doi.org/10.1016/j.ejr.2016.10.003
1110-1164/ 2016 Egyptian Society of Rheumatic Diseases. Publishing services provided by Elsevier B.V.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Peer review under responsibility of Egyptian Society of Rheumatic Diseases.
⇑ Corresponding author at: Department of Internal Medicine, Hospital Universi-
tario de Fuenlabrada, Camino del Molino, 2, 28942 Fuenlabrada, Madrid, Spain.
E-mail address: miguelangel.duarte@salud.madrid.org (M.A. Duarte-Millán).
Please cite this article in press as: Duarte-Millán MA et al. Reversed halo sign as initial manifestation of interstitial pneumonitis associated with Sj
syndrome. The Egyptian Rheumatologist (2016), http://dx.doi.org/10.1016/j.ejr.2016.10.003M.A. Duarte-Millán a,⇑, D. Bernal-Bello a, J.A. Rueda-Camino a, S. Martín-Barón b, J. Canora-Lebrato a,
A. Zapatero-Gaviria a
aDepartment of Internal Medicine, Hospital Universitario de Fuenlabrada, Madrid, Spain
bDepartment of Radiology, Hospital Universitario de Fuenlabrada, Madrid, Spaina r t i c l e i n f o
Article history:
Received 17 October 2016
Accepted 23 October 2016
Available online xxxx
Keywords:
Sjögren’s syndrome
Reversed halo sign
Interstitial pneumonitis
Organizing pneumoniaa b s t r a c t
Introduction: Sjögren’s syndrome (SS) is a chronic autoimmune multisystemic disease. Respiratory man-
ifestations of SS are polymorphic and vary in severity. Among the possible manifestations, organizing
pneumonia (OP) is a rare entity. Reversed halo sign (RHS) is an unusual radiological finding classically
related to OP but it is also reported in other forms of interstitial pneumonitis (IP).
Case presentation: We report a case of a 65-year-old woman with dyspnoea and persistent-cough of 2-
month duration. She presented with RHS as an initial manifestation of IP related to SS. Chest radiography
and computer tomography showed multiple well defined lesions with a central ground glass area and
peripheral rim of consolidation. No pathological lymph nodes were found. After investigations, the asso-
ciated diagnosis of SS was confirmed. The patient started steroids (0.5 mg/kg/day) and after 10 weeks of
steroid tapering a significant clinical improvement was observed, with radiological resolution of lung
lesions. We make some general considerations about differential diagnosis, conditions related to RHS
and different patterns of lung involvement in SS. A report of the literature emphasizes this case as an
exceptional way of presentation.
Conclusion: To the best of our knowledge this is the second reported OP case associated with SS manifest-
ing as RHS. RSH as an expression of IP related to SS is exceptional, either in the pattern of OP or non-
specific IP.
 2016 Egyptian Society of Rheumatic Diseases. Publishing services provided by Elsevier B.V. This is an
open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).1. Introduction
Sjögren’s syndrome (SS) is a chronic autoimmune multisys-
temic disease featured by progressive dysfunction of exocrine
glands due to lymphocytic infiltration [1]. SS is the second most
common autoimmune disease after rheumatoid arthritis (RA).
The prevalence of clinically significant lung disease in SS is 9–
20% with a female predominance. Respiratory manifestations of
SS are polymorphic and vary in severity, explaining this wide vari-
ability of prevalence [2]. SS is associated with interstitial pneu-
monitis (IP) which can also be the first manifestation of the
disease, resulting in impaired quality of life and decreased survival.
Among IP secondary to SS, organizing pneumonia (OP) is a rela-
tively rare disorder compared to other patterns such as nonspecificinterstitial pneumonia (NSIP), usual interstitial pneumonia (UIP) or
lymphocytic interstitial pneumonia (LIP).
Connective tissue diseases (CTD) are known to be one of the
causes of OP. However, this association is rare and signs of OP usu-
ally occur in the context of an already diagnosed disease. It has
been suggested that exhaustive investigations should be consid-
ered when OP is diagnosed, including antinuclear antibodies
(ANA) and investigations for SS, even when there are no clinical
signs suggesting an underlying CTD [3]. Even though the associa-
tion of COP with primary SS is extremely rare it may be an early
manifestation [4]. It has been reported that no remarkable differ-
ences in clinical and radiologic manifestations were present
between patients with cryptogenic organizing pneumonia (COP)
and those with CTD related OP (CTD-OP), except that the propor-
tion of women and ANA positive rate were higher in CTD-OP
including those with SS [5].
The unusual presence of a focal ring-shaped area of ground-
glass opacity within a peripheral rim of consolidation called
reversed halo sign (RHS) or atoll sign is a radiological findingögren’s
2 M.A. Duarte-Millán et al. / The Egyptian Rheumatologist xxx (2016) xxx–xxxstrongly suggestive but no exclusive of OP. We report a case of SS
presenting with RHS.1.1. Case report
A 65-year-old woman with no significant medical history born
at the Dominican Republic but living for more than 10 years in
Spain with no recent travels, was admitted to our Department with
dyspnoea and persistent-cough of 2-month duration. She denied
haemoptysis, fever, chest pain or weight loss. No digestive, articu-
lar or urinary symptoms were developed. Her clinical examination
on admission was unremarkable. The patient gave an informed
consent in accordance with the Declaration of Helsinki.
Chest radiography and computer tomography showed multiple
well defined lesions with a central ground glass area and periph-
eral rim of consolidation, showing the RHS pattern (Fig. 1a and
b). No pathological lymph nodes were found.
No laboratory findings were noted in the complete blood count,
liver and renal functions or coagulation. Elevated erythrocyte sed-
imentation rate (ESR: 73 mm/1st hour, normal 0–30 mm/1st) and
C reactive protein level (CRP: 1.22 mg/dL, normal 0.1–0.5 mg/dL)
were observed. Immunoglobulin G level was also high (1909 mg/
dL, normal: 700–1600 mg/dL) and serum protein electrophoresis
showed a gammaglobulin polyclonal increase. Serological tests
for human immunodeficiency virus, cytomegalovirus, Epstein-Barr
virus, hepatitis C virus and Toxoplasma were all negative. Past hep-
atitis B infection was found.
A bronchoscopy was performed without noteworthy results.
Microbiological tests in sputum, bronchoalveolar lavage and bron-
chial aspirate (including Gram staining, auramine-rodamine, direct
exam for fungi and P. jiroveci detection) were all negative. A Para-
coccidiodides brasiliensis polymerase chain reaction (PCR) in bron-
chial aspirate sample was also negative. While performing
transbronchial biopsy whose results were ultimately inconclusive,
iatrogenic pneumothorax was developed so we desist from making
a new attempt to get histological samples.
Antinuclear antibody (ANA) screening (1:160) and anti-Ro/SS-A
were positive, with normal levels of C3-C4 complement, cryoglob-
ulins, anti-neutrophil cytoplasmic antibody and angiotensin con-
verting enzyme (ACE). Based on this antibody profile, the patient
was asked about dry eye or dry mouth previous history. She admit-Figure 1. (a). Chest radiography and (b). CT scan shows RHS, a central gro
Please cite this article in press as: Duarte-Millán MA et al. Reversed halo sign a
syndrome. The Egyptian Rheumatologist (2016), http://dx.doi.org/10.1016/j.ejrted presence of long-standing xerostomia and xerophthalmia had
never been studied. Schirmer’s test was positive and reduced glo-
bal saliva secretion was demonstrated by gammagraphy. Diagnosis
of SS was established according to the revised version of classifica-
tion criteria [6].
Taking into account the previous findings and patient’s
immunocompetent status, SS associated IP was suspected and
prednisone 0.5 mg/kg/day was started. Neither antibiotics nor anti-
fungals were added to treatment. After 10 weeks of steroid taper-
ing a significant clinical improvement was observed, with
radiological resolution of lung lesions.2. Discussion
The lack of histological confirmation is a serious limitation to
ensure the diagnosis in this case. However, we would perform
some diagnostic considerations in view of clinical and radiological
evolution with steroid treatment (strategy suggested by some
authors when histology or focused investigations are inconclusive
or cannot be obtained) [7]. In a previously reported case, typical
bilateral pulmonary shadows were confirmed as OP by the analysis
of bronchoalveolar lavage fluid and transbronchial lung biopsy [8].
Reversed halo sign was first reported in cryptogenic OP and ini-
tially considered a hallmark of this disease [9]. Ulterior publica-
tions widened the spectrum of conditions associated to this sign
[10]. Tuberculosis and some fungal diseases are remarkable infec-
tions related to RHS, among which Paracoccidioides is singularly
important in patients from Latin America and the Caribbean [11].
In our case, infectious diseases were reasonably ruled out due to
microbiological negative results, patient’s immunocompetent sta-
tus and favourable response to prednisone.
Regarding non-infectious causes, sarcoidosis seems an unlikely
diagnosis due to normal ACE and lack of lymphadenopathy or
nodular appearance of ring area. Otherwise, presentation and clin-
ical evolution was not compatible with vasculitis or malignancy.
Finally, our case fulfilled the classification criteria for Sjögren’s
syndrome.
Data from the largest cohort of SS [12] showed NSIP was the
most prevalent pattern of IP followed by UIP and LIP, while OP
was only present in 7% of patients. RHS was not observed in this
cohort so it may be considered an uncommon radiological finding.und-glass opacity surrounded by a ring-shaped area of consolidation.
s initial manifestation of interstitial pneumonitis associated with Sjögren’s
.2016.10.003
M.A. Duarte-Millán et al. / The Egyptian Rheumatologist xxx (2016) xxx–xxx 3However, a recent review concluded that OP still remains as the
most common IP associated with RHS [7]. Therefore, in the absence
of conclusive histology we consider that presence of RHS suggests
more strongly the OP diagnosis given its lower association to NSIP.
The present case showed a significant clinical and radiological
improvement after 10 weeks of tapering steroids. Similarly, a
patient with COP associated SS improved on steroids. It was recom-
mended that exclusion of SS should be part of a thorough evalua-
tion of patients with COP [4]. Again, high dose steroid treatment
resulted in resolution of symptoms and prolonged remission in a
case with sicca complex associated with OP [13]. However, it has
been suggested that in refractory cases with OP associated with
SS, tocilizumab could be an alternative therapeutic option [14].
To the best of our knowledge only one OP case secondary to SS
manifesting as RHS has been previously reported [15]. Also one
case of RHS related to NSIP has been described in a patient with
SS-systemic sclerosis overlap [16]. In summary, RSH as an expres-
sion of IP related to SS is exceptional, either in the pattern of OP or
NSIP.
Conflict of interest
None.
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Reversed halo sign as initial manifestation of interstitial pneumonitis associated with Sjögren’s syndrome

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