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Diagnosing Rosacea


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Obtaining a diagnosis for rosacea may seem to be fairly straight forward but considering that there are reports of misdiagnosis it would be good for rosaceans to be educated on this subject so that if one experiences a misdiagnosis it will not be a surprise and will understand better how a diagnosis is obtained. A survey by Galderma/NRS says that the results [of a unique digital perception survey] “highlight the low awareness and complicated diagnosis path for this common condition.” Are you aware of how a diagnosis of rosacea is obtained?

Generally, one diagnostic differentiator is when treatments for acne exacerbate the problem, this is used as an indicator in a diagnosis of rosacea. Rosacea is sometimes referred to as  'adult acne' in older papers, later called 'acne rosacea' and because it looks like acne. Rosacea is generally adult onset, and older adults obtaining a rosacea diagnosis is common. However, there are now reports of children receiving a diagnosis of rosacea. [24]

First and foremost is that diagnosis is the sole prerogative legally and ethically of a physician, not obtained in rosacea social media groups

So the information in this editorial is not meant to substitute or replace a physician’s diagnosis but is simply for a rosacea sufferer to understand the subject of a rosacea diagnosis for educational purposes. Knowing what is involved in obtaining a diagnosis of rosacea is quite helpful in basic Rosacea 101 which is a subject I am quite familiar with and wish to pass on this information freely to those who wish to increase their rosacea knowledge. When you read in rosacea social media groups the common question, 'IS THIS ROSACEA?' asked to a group of rosacea sufferers by posting photos of your face, do you really think that this group is qualified to differentiate rosacea from this list? However, learning how a diagnosis of rosacea is obtained by a physician can be rewarding and help you better to ask pertinent questions to your dermatologist. 

The NRS Classification System (2002) into subtypes and one variant is the first clearly defined proposal to identify and classify rosacea. [2] It is of interest to note that this classification system is based on morphology rather than causality. Understanding this classification and variant system was the beginning of a better understanding for this disease, however, it has been controversial from the beginning. Dermatologists who are still using the subtype classification system are somewhat able to better diagnose rosacea and it may be that your physician is familiar with this old classification, however, some physicians are not keeping up with this latest classification system, the phenotype classification, and may be relying on past knowledge on this subject when referring to subtypes. If your physician is still referring to subtypes, you may want to point out the next paragraph to your physician. 

Phenotype Classification of Rosacea
The new direction of classifying rosacea is a phenotype based treatment.

"Because rosacea can encompass a multitude of possible combinations of signs and symptoms, the following updated classification system is based on phenotypes—observable characteristics that can result from genetic and/or environmental influences—to provide the necessary means of assessing and treating rosacea in a manner that is consistent with each individual patient's experience. The phenotypes and diagnostic criteria are largely in agreement with those recommended by the global rosacea consensus panel in 2016, and at least 1 diagnostic or 2 major phenotypes are required for the diagnosis of rosacea." [15]

Physical Examination, History & Tests

Does rosacea spread beyond the facial region?

There are no generally accepted histological, serological or other diagnostic tests for rosacea, therefore, a diagnosis is simply arrived at by a patient history and physical examination. [1] However, rosaceans have been shown to have high serum zonulin levels. [14] [17] Some clinical tests may be done, i.e., blood tests, skin biopsies, scans, etc., to rule out rosacea mimics or other diseases, not to mention ruling out other co-existing conditions. One report recommends thyroid tests. [19]

Frank Powell, MD, who served on the NRS ‘expert committee‘ that classified rosacea says in his book, “There is no laboratory test or investigation that will confirm the diagnosis of PPR. Specific investigations may be required to rule out similar appearing conditions (many of which will be identified by listening carefully to the patient’s medical history and examining the skin lesions). These include skin swabs for bacterial culture, skin scrapings for the presence of demodex mites, scrapings for fungal KOH and fungal culture, skin biopsy for histologic examination, (and rarely culture) skin surface biopsy for demodex mite quantification, patch tests, photopatch tests, and very rarely systemic workup with appropriate blood tests and radiological examinations.” [3]

There are now certain devices recommended to be more objective in diagnosing rosacea, i.e., non-invasive imaging and measurement tools. [12]

To rule out demodectic rosacea “Potassium hydroxide examination, standardized skin surface biopsy, skin biopsy, or a combination of these are essential to establish the diagnosis.” [4] However, some researchers state that  if you use a skin scraping with a light microscope, there may be no reliable data on demodex density counts. However when using a 'Confocal laser scanning in vivo microscopy', there is a significantly more reliable data to count on simply using a skin scraping with a microscope. [11]

In some cases to rule out rosacea mimics such as lupus and scleroderma it is suggested that obtaining an ANA blood test and other blood tests might be considered. [5] Another test you might consider having is the Autologous serum skin test (ASST) to rule out chronic uticaria.

One report says it is necessary to perform individual bacterial cultures and antibiograms on rosacea patients. [6]

Another report suggests testing mucin to differentiate lupus. [7]

Another test to consider is to rule out Grave’s disease with blood tests. According to Ladonna, “…my husband took me to the dermatologist and she said it was Rosacea and couldnt be anything but….So he took me to many doctors, and finally a wonderful doctor took a shot in the dark blood test and discovered my problem. Later more involved tests and scans confirmed it. I was Hyperthyroid…specifically Graves Disease…”

So from the above tests it shows that a five minute visit to your dermatologist who simply diagnoses you with rosacea and doesn’t take any of the tests mentioned above to differentiate other rosacea mimics might mean you could receive a misdiagnosis. There is anecdotal evidence that many rosaceans report a quick diagnosis in five minutes or less.

Galderma has patented a diagnostic test for rosacea

"Facial erythema, the most common primary feature of all subtypes of rosacea, has been described as a mandatory diagnostic feature and is thus the predominant mark of patients with rosacea, especially in the ETR and PPR subtypes, but it can also be present in PhR and OR." [13]

Serum Zonulin Level have been shown high in rosacea patients. [17]

"abnormally high facial skin levels of cathelicidin and the trypsin-like serine protease kallikrein 5 (KLK5)" [18]

GPSkin® Barrier Device

One report recommends thyroid tests and states, "Our findings indicate that thyroid blood tests, including thyroid autoantibodies, should be tested and thyroid ultrasounds should be performed in patients diagnosed with rosacea." [19]

"Erythema, burning, dryness and itching are the characteristics of papulopustular rosacea, which makes it different from acne vulgaris. The epidermal barrier function was damaged in papulopustular rosacea patients while not impaired in that of acne vulgaris patients." ]21]

"Recent research has confirmed the increased presence of bacterial genera like Acidaminococcus and Megasphera in the intestinal microbiome and Rheinheimera and Sphingobium in the blood microbiome of rosacea patients." [22]

"five accurate CNNs-based evaluation system (FACES)" [25]

There are a number of other skin diseases that mimic rosacea and should be ruled out in a Differential Diagnosis Of Rosacea.

Taking a Patient History and Biopsies

In Powell’s last chapter, [3] entitled, General Considerations, he suggests asking questions to the patient in taking a history, specifically:

(1) Asking about polycythemia?

(2) Whether the patient has been using a steroid cream?

(3) Any other medication such as niacin or antacids?

(4) Whether there has been any frequent flushing?

(5) Any complementary or alternative medicines, i.e., herbal products?

(6) Eye symptoms?

(7) Any family history of rosacea?

Biopsies to rule out demodectic rosacea is another important consideration. One report suggests a biopsy to rule out Morbus Morbihan.

If you physician neglects to ask any of the above questions you might simply bring the above questions to his attention in a respectful tone so that a proper diagnosis of your skin condition can be obtained. Not knowing the answers to the above questions may hinder a proper diagnosis.

Rosaceanet (ADD) has 15 questions to ask you and then recommends something to you if you would like more info on a diagnosis. [8] If you note the disclaimer it says, "This questionnaire does not provide medical advice. It should not be used to diagnose rosacea. Only a medical doctor such as a dermatologist can make this diagnosis. The purpose of this questionnaire is to help you seek medical care if you believe that you may have rosacea. A dermatologist can provide you with a diagnosis and proper treatment."

"Central facial redness affects many adults and can be an indicator of the chronic inflammatory disease rosacea. Rosacea is a clinical diagnosis based on the patient’s history, physical examination, and exclusion of other disorders." [16]

Dermoscopy and Other Tools to Detect or Quantify Demodex Density Counts

Dermoscopy may prove useful according to this source:

"Dermoscopy, in addition to its well-documented value in evaluation of skin tumours, is continuously gaining appreciation also in the field of general dermatology." [9] "The dermoscopic hallmark of rosacea is represented by the presence of linear vessels characteristically arranged in a polygonal network (vascular polygons) {click for image}." [10]

Scroll down to the subheading, Tools to Detect or Quantify Demodex Density Counts, in the post, Demodex Density Count - What are the Numbers?

Polarized Light Dermoscopy to test for Rosetts

"There are also isolated reports of the presence of rosettes in a lesion of discoid lupus erythematosus and in papulopustular rosacea." [20]

Non-Invasive Object Skin Measurement
A study recommends a more objective skin measurement for erythema, demodex density counts, rosacea severity, etc, using certain device tools. [12]

Serum Zonulin Level Measurement
The serum zonulin levels were found to be significantly higher in patients with acne rosacea. [14]

Skin Hydration Sensor (SHS)
A device to assist dermatologists which "measures volumetric water content (up to ~1 mm in depth) and wirelessly transmits data to any near-field communication–compatible smartphone." [23] Whether this device assists in diagnosing rosacea remains to be seen. 

Etcetera

Tests to Differentiate Rosacea

Diagnosing Rosacea In Five Minutes Or Less

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End Notes

[1] National Rosacea Society, Answer to Question 5
http://www.rosacea.org/patients/faq.php#test

"There is no appropriate and reliable method of evaluating and monitoring severity in rosacea."
Nailfold capillaroscopy as a diagnostic and prognostic method in rosacea.
Fonseca GP, Brenner FM, Muller CD, Wojcik AL.
An Bras Dermatol. 2011 Feb;86(1):87-90.

[2] Classification of Rosacea
http://www.rosacea.org/class/classysystem.php

[3] Rosacea Diagnosis and Management by Frank Powell
with a Contribution by Jonathan Wilkin

[4] Demodicosis: a clinicopathological study.
Hsu CK, Hsu MM, Lee JY.
J Am Acad Dermatol. 2009 Mar;60(3):453-62

[5] Scroll to Alba’s Post #6 about ANA Blood Tests

[6] Necessary to perform individual bacterial cultures and antibiograms in rosaceans?

A new study on acne and rosacea patients concluded these findings:

CONCLUSIONS:
1. In the cases of acne vulgaris the majority of isolated bacteria from conjunctival sac included Streptococcus spp., Staphylococcus spp. and Enterobacteriaceae.
2. In the severe cases of rosacea the main bacteria found in conjunctival sac were S. aureus, S.pyogenes, P.aeruginosa, E. faecalis, A. baumanii, P. fluorescens.
3. Because of changeable drug-sensitivity of bacterial strains, it seems to be necessary to perform individual culture and antibiogram in every patient with inflammatory lesions, in particular in clinically severe and resistant to therapy cases of acne vulgaris and rosacea.
4. The higher frequency of the bacterial colonisations in the conjunctival sac in patients with acne vulgaris and rosacea can be a potential source of ocular infections in the cases of local and systemic disorders of protective mechanisms.
5. Estimation of bacterial flora and antibiotic sensitivity of bacteria isolated from conjunctival sac, the skin of the eyelids and skin lesions should be perform, especially when patients are prepared for eye surgery.

Source of the above information

[7] Mucin is not a rare finding in rosacea is the title of a research study done by A. Fernandez-Flores at the Service of Cellular Pathology, Clinica Ponferrada in Spain.

http://www.ncbi.nlm.nih.gov/pubmed/20191122?dopt=Abstract

http://www.clinicaponferrada.com/

Mucins are a family of high molecular weight, heavily glycosylated proteins (glycoconjugates) produced by epithelial tissues in most metazoans. They are being investigated for their potential as diagnostic markers.

http://en.wikipedia.org/wiki/Mucin

The study concluded "that: 1. mucin is a common finding in granulomas of rosacea; 2. this mucin is probably not related to any progression to the mucinous variant of rhinophyma; 3. since discoid erythematosus lupus is a clinical differential of rosacea, it is important to be aware of the fact that
mucin is a common finding in the granulomas, in order not to misdiagnose both entities."

Here is another potential diagnostic marker to differentiate rosacea from lupus.

[8] Rosaceanet
American Academy of Dermatology
Could I Have Rosacea?

[9] J Eur Acad Dermatol Venereol. 2013 Mar 12. doi: 10.1111/jdv.12146. [Epub ahead of print]
Dermoscopic patterns of common facial inflammatory skin diseases.
Lallas A, Argenziano G, Apalla Z, Gourhant JY, Zaballos P, Di Lernia V, Moscarella E, Longo C, Zalaudek I.

[10] Dermatol Ther (Heidelb). 2016 Dec; 6(4): 471–507.
Published online 2016 Sep 9. doi:  10.1007/s13555-016-0141-6
PMCID: PMC5120630
Dermoscopy in General Dermatology: A Practical Overview
Enzo Errichetti, Giuseppe Stinco

[11] Russian Study on Demodex Mites and Rosacea Illuminating

[12] Br J Dermatol. 2019 May 23;:
Non-invasive objective skin measurement methods for rosacea assessment: a systematic review.
Logger JGM, de Vries FMC, van Erp PEJ, de Jong EMGJ, Peppelman M, Driessen RJB

[13] ebcd2834a10dd16de29012a02f3129a9a92f.pdf

[14] J Dermatolog Treat. 2020 Apr 15;:1-13
Measurement of the serum zonulin levels in patients with acne rosacea.
Yüksel M, Ülfer G

[15] Standard classification and pathophysiology of rosacea: The 2017 update by the National Rosacea Society Expert Committee

[16] Recognizing Rosacea: Tips on Differential Diagnosis
September 2019 | Volume 18 | Issue 9 | Original Article | 888 | Copyright © September 2019
Sandra Marchese Johnson MD FAAD, Andrew Berg PA, Chelsea Barr MPAS PA-C
ebcd2834a10dd16de29012a02f3129a9a92f.pdf

[17] J Dermatolog Treat. 2020 Apr 23;1-4.  doi: 10.1080/09546634.2020.1757015. 
Measurement of the Serum Zonulin Levels in Patients With Acne Rosacea
Mavişe Yüksel, Gözde Ülfer 

[18] Exp Dermatol. 2014 Jul 21;
Endoplasmic reticulum stress: key promoter of rosacea pathogenesis.
Melnik BC

[19] Dermatol Ther. 2020 Dec 05;:
investigation of thyroid blood tests and thyroid ultrasound findings of patients with rosacea.
Gönülal M, Teker K, Öztürk A, Yaşar FY

[20] An Bras Dermatol. 2020 Nov 16;S0365-0596(20)30297-X. doi: 10.1016/j.abd.2020.05.010.  PubMed
Rosettes in T-cell pseudolymphoma: a new dermoscopic finding
Rodrigo Gomes Alves, Patricia Mayumi Ogawa, Mílvia Maria Simões E Silva Enokihara, Sergio Henrique Hirata  

[21] Pak J Med Sci. Nov-Dec 2016;32(6):1344-1348.  doi: 10.12669/pjms.326.11236.
Clinical characteristics and epidermal barrier function of papulopustular rosacea: A comparison study with acne vulgaris
Maosong Zhou, Hongfu Xie, Lin Cheng, Ji Li  

[22] Acta Microbiol Immunol Hung. 2021 Jan 29;:
Interactions between immune system and the microbiome of skin, blood and gut in pathogenesis of rosacea.
Joura MI, Brunner A, Nemes-Nikodém É, Sárdy M, Ostorházi E

[23] Skin Hydration Sensor (SHS) 
The device is "a soft, battery-free, noninvasive, reusable skin hydration sensor (SHS) adherable to most of the body surface. The platform measures volumetric water content (up to ~1 mm in depth) and wirelessly transmits data to any near-field communication–compatible smartphone. The SHS is readily manufacturable, comprises unique powering and encapsulation strategies, and achieves high measurement precision (±5% volumetric water content) and resolution (±0.015°C skin surface temperature)."

The article does mention rosacea once here: 

"Key results include clinical use of the SHS on n = 13 patients with a wide range of inflammatory skin conditions (e.g., AD, psoriasis, urticaria, xerosis cutis, and rosacea), with benchmarks against standard tools to quantitatively characterize the diseased locations."

Whether this device can be used to assist dermatologists with rosacea remains to be seen. 

Sci Adv. 2020 Dec; 6(49): eabd7146.
Reliable, low-cost, fully integrated hydration sensors for monitoring and diagnosis of inflammatory skin diseases in any environment
Surabhi R. Madhvapathy, Heling Wang, Jessy Kong, Michael Zhang, Jong Yoon Lee, Jun Bin Park, Hokyung Jang, Zhaoqian Xie, Jingyue Cao, Raudel Avila, Chen Wei, Vincent D’Angelo, Jason Zhu, Ha Uk Chung, Sarah Coughlin, Manish Patel, Joshua Winograd, Jaeman Lim, Anthony Banks, Shuai Xu, Yonggang Huang, John A. Rogers

[24] PubMed RSS Feed - -Deciphering Childhood Rosacea: A Comprehensive Review

[25] PubMed RSS Feed - -FACES: A Deep-Learning-Based Parametric Model to Improve Rosacea Diagnoses

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"To date, the diagnosis of rosacea has been established clinically based on observation and interpretation of skin and ocular signs."

Mol Vis. 2021; 27: 323–353.
Cutaneous and ocular rosacea: Common and specific physiopathogenic mechanisms and study models
Daniela Rodrigues-Braz, Min Zhao, Nilufer Yesilirmak, Selim Aractingi, Francine Behar-Cohen, Jean-Louis Bourges

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