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Sarcoidosis vs. Sarcoid-like reactions: The Two Sides of the same Coin?

Sarkoidose versus sarkoidale Reaktionen: Zwei Seiten einer Medaille?

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Summary

Differentiating between sarcoidosis as an autonomous disease and sarcoid-like reactions requires considerable efforts. The epithelioid cell granuloma is not equivalent to sarcoidosis because it may be identified in a number of infectious and noninfectious disorders, including neoplastic diseases. At the current state of knowledge, accurate distinction between different causes of epithelioid cell granulomas is in many cases not possible. Despite being characteristic of sarcoidosis and sarcoid-like reactions, the epithelioid cell granuloma is not their synonym, as numerous other causes can give rise to such a type of granulomatous infiltrate. Its etiology should be sought through careful additional investigations, including the genetic signature of both conditions.

Sarcoid-like reactions may be grouped generally into several subtypes. The differentiation between each one of them requires a certain combination of diagnostic tests. The major objective of these tests is to exclude or to prove the presence of an infectious, tumoral, or immunogenic antigen on the one hand, and to characterize the genetic profile of the affected patients (for example, sarcoidosis-specific genes) on the other. Only thus may one accurately differentiate between the two pathologic conditions described earlier in the abstract.

The clear differentiation between sarcoidosis as a separate disease and sarcoid-like pathologies leads to the more precise clarification of the final diagnosis, which may in turn allow for a more appropriate therapy and improvement in the quality of life of the patients. Equating sarcoid granulomas with sarcoidosis can lead to serious consequences in a number of patients. Sadly enough, after scrutinizing the current available data in the world literature, one cannot find criteria to allow such distinction in a high percentage of the investigated cases.

This critical review provides a completely new pathogenetic and diagnostic algorithm, helping in the differentiation between the disease sarcoidosis and the sarcoid-like pathologies with different etiology. An update on the inclusion criteria from the ATS/ERS/WASOG (American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and other Granulomatous Disorders) statement (which at the current state of knowledge seems to be ineffective) for the diagnosis of sarcoidosis is also suggested.

In conclusion, molecular mimicry may be seen as the main pathogenic generator not only of sarcoidosis but also of sarcoid-like reactions. A completely new and exact definition of the notion of or the sarcoidosis disease itself will be possible only after

  1. 1.

    defining the genetic risk for the development of sarcoidosis as an autonomous disease and supplementing the sarcoidosis consensus of ATS/ERS/WASOG from 1999 with this important information, and

  2. 2.

    defining the notion of a sarcoid-like reaction and its subforms.

Zusammenfassung

Die Unterscheidung von Sarkoidose als eigenständiger Erkrankung und sarkoidaler Reaktion erfordert erhebliche Anstrengungen. Der Nachweis epitheloidzelliger Granulome ist nicht der Diagnose einer Sarkoidose gleichzusetzen, da diese bei einer Vielzahl von infektiösen und nicht infektiösen Erkrankungen, einschließlich der Tumore, auftreten können. Mit unserem derzeitigen Wissensstand ist die exakte Differenzierung bezüglich ihrer Ursachen aus nicht immer möglich. Obwohl die epitheloidzelligen Granulome charakteristisch für Sarkoidose und sarkoidale Reaktionen sind, können zahlreiche andere Ursachen für ihre Entstehung verantwortlich sein. Ihre Ätiologie sollte durch sorgfältige zusätzliche Untersuchungen einschließlich der genetischen Signatur beider Erkrankungen geklärt werden.

Sarkoidale Reaktionen können in verschiedene Subtypen klassifiziert werden. Deren Unterscheidung bedarf einer gewissen Kombination der Untersuchungsverfahren. Hauptanliegen dieser Untersuchungen ist die Verifizierung bzw. der Ausschluß infektiöser, tumoraler oder immunogener Antigene einerseits und die Beschreibung des genetischen Profils des betroffenen Patienten (z.B. sarkoidose-spezifische Gene) andererseits. Nur hierdurch wird eine exakte Differenzierung beider Pathologien (Sarkoidose, sarkoidal) möglich.

Die eindeutige Differenzierung von Sarkoidose und sarkoidaler Reaktion als verschiedene Erkrankungen erlaubt eine präzisere Diagnose, eine zielgerichtetere Behandlung und die Verbesserung der Lebensqualität der Patienten. Umgekehrt kann die Nichtbeachtung dieses Grundsatzes zu ernsten Konsequenzen für betroffene Patienten führen. Leider ist bietet die wissenschaftliche Weltliteratur bislang keine Kriterien, die eine klare Unterscheidung beider Pathologien bei einem hohen Prozentsatz der Patienten erlaubt.

Diese kritische Übersicht entwickelt einen komplett neuen pathogenetischen und diagnostischen Algorithmus zur Differenzierung von Sarkoidose und sarkoidaler Reaktion verschiedener Ätiologien. Ein Update der Einschlußkriterien der ATS/ERS/WASOG (American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and other Granulomatous Disorders) für die Sarkoidose-Diagnose wird ebenfalls vorgeschlagen.

Schlußfolgerungen: Molekulare Mimikry kann als wesentlicher Motor nicht allein für die Sarkoidose, sondern auch die sarkoidale Reaktion angesehen werden. Eine komplett neue und exakte Definition der Diagnose Sarkoidose wird nur dann möglich werden, wenn:

  1. 1.

    Das genetische Risiko der Sarkoidoseentwicklung bestimmt und der Konsensus der ATS/ERS/WASOG von 1999 implementiert wird.

  2. 2.

    Die sarkoidale Reaktion und ihre Subtypen bestimmt werden.

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Article 04 July 2019

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Authors and Affiliations

  1. Policlinic for Dermatology and Venerology, University Hospital Lozenetz, Medical Faculty, Saint Kliment Ohridski University, Koziak Street 1, 1407, Sofia, Bulgaria

    Georgi Tchernev

  2. Department of Medicine and Science of Aging, “G. d’Annunzio” University, Chieti, Italy

    Claudio Tana MD, PhD &  Cosima Schiavone

  3. Dermatology Department, University Hospital of Coimbra, Praceta Mota Pinto, 3000 075, Coimbra, Portugal

    José-Carlos Cardoso MD, PhD

  4. Department of General and Clinical Pathology,Medical Faculty, Trakia University, Armeiska Str 11, 6000, Stara Zagora, Bulgaria

    Julian Ananiev MD, PhD

  5. Allergology & Environmental Medicine, Hospital Dresden-Friedrichstadt, Academic Teaching Hospital, Technical University of Dresden, Friedrichstrasse 41, 01067, Dresden, Germany

    Uwe Wollina MD

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  1. Georgi Tchernev
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  2. Claudio Tana MD, PhD
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  3. Cosima Schiavone
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  4. José-Carlos Cardoso MD, PhD
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  5. Julian Ananiev MD, PhD
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Correspondence to Georgi Tchernev.

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Tchernev, G., Tana, C., Schiavone, C. et al. Sarcoidosis vs. Sarcoid-like reactions: The Two Sides of the same Coin?. Wien Med Wochenschr 164, 247–259 (2014). https://doi.org/10.1007/s10354-014-0269-x

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  • DOI: https://doi.org/10.1007/s10354-014-0269-x

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