Major Pathophysiological Correlations of Rosacea: A Complete Clinical Appraisal
Identifieur interne : 007411 ( Ncbi/Merge ); précédent : 007410; suivant : 007412Major Pathophysiological Correlations of Rosacea: A Complete Clinical Appraisal
Auteurs : Ravi Chandra Vemuri [Malaisie] ; Rohit Gundamaraju [Malaisie] ; Shamala Devi Sekaran [Malaisie] ; Rishya Manikam [Malaisie]Source :
- International Journal of Medical Sciences [ 1449-1907 ] ; 2015.
Abstract
Url:
DOI: 10.7150/ijms.10608
PubMed: 26005373
PubMed Central: 4441063
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Major Pathophysiological Correlations of Rosacea: A Complete Clinical Appraisal</title>
<author><name sortKey="Vemuri, Ravi Chandra" sort="Vemuri, Ravi Chandra" uniqKey="Vemuri R" first="Ravi Chandra" last="Vemuri">Ravi Chandra Vemuri</name>
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<author><name sortKey="Gundamaraju, Rohit" sort="Gundamaraju, Rohit" uniqKey="Gundamaraju R" first="Rohit" last="Gundamaraju">Rohit Gundamaraju</name>
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<author><name sortKey="Sekaran, Shamala Devi" sort="Sekaran, Shamala Devi" uniqKey="Sekaran S" first="Shamala Devi" last="Sekaran">Shamala Devi Sekaran</name>
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<author><name sortKey="Manikam, Rishya" sort="Manikam, Rishya" uniqKey="Manikam R" first="Rishya" last="Manikam">Rishya Manikam</name>
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<series><title level="j">International Journal of Medical Sciences</title>
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<front><div type="abstract" xml:lang="en"><p><bold>Background</bold>
: Rosacea is a characteristic cutaneous disorder with a diverse clinical manifestations ranging from facial vascular hyper-reactivity to sebaceous gland hyperplasia. Many theories on pathophysiology of rosacea were proposed over the past decade, however the pathogenicity is poorly understood.</p>
<p><bold>Aim: </bold>
To review the evidence on different pathophysiological correlations of rosacea.</p>
<p><bold>Methods: </bold>
A literature search was conducted for studies published between 1990 to March 2014. The inclusion criteria was pathophysiology, randomized controlled trials, controlled trials on rosacea.</p>
<p><bold>Results: </bold>
Out of 5141 articles, 14 high quality studies met all the selection criteria. Of 14 articles, 5 are randomized control trials (RCTs), 2 are controlled trial, 3 comparative trials, 2 observational trials, 1 prospective and 1 diagnostic trial. The studies were categorized into two groups: the trigger factors and sub-types & symptoms. Of 7 high quality studies, 4 provided strong evidence that immune responses causing disease triggered by external/internal factors such as sunlight, food and chemical agents, 3 trials provided significant evidence of microorganisms as causative agents. The remaining trials did not provide significant evidences on pathophysiology.</p>
<p><bold>Conclusion: </bold>
Vasculature, chronic inflammatory responses, environmental triggers, food and chemicals ingested and microorganisms either alone or in combination are responsible for rosacea. Many promising drugs are under various phases of clinical trials and interestingly, probiotics could also possibly be used as one of the treatment option.</p>
</div>
</front>
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<pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Int J Med Sci</journal-id>
<journal-id journal-id-type="iso-abbrev">Int J Med Sci</journal-id>
<journal-id journal-id-type="publisher-id">ijms</journal-id>
<journal-title-group><journal-title>International Journal of Medical Sciences</journal-title>
</journal-title-group>
<issn pub-type="epub">1449-1907</issn>
<publisher><publisher-name>Ivyspring International Publisher</publisher-name>
<publisher-loc>Sydney</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">26005373</article-id>
<article-id pub-id-type="pmc">4441063</article-id>
<article-id pub-id-type="doi">10.7150/ijms.10608</article-id>
<article-id pub-id-type="publisher-id">ijmsv12p0387</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Review</subject>
</subj-group>
</article-categories>
<title-group><article-title>Major Pathophysiological Correlations of Rosacea: A Complete Clinical Appraisal</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Vemuri</surname>
<given-names>Ravi Chandra</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="corresp" rid="FNA_envelop">✉</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gundamaraju</surname>
<given-names>Rohit</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sekaran</surname>
<given-names>Shamala Devi</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="corresp" rid="FNA_envelop">✉</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Manikam</surname>
<given-names>Rishya</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
</contrib-group>
<aff id="A1">1. Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia</aff>
<aff id="A2">2. Department of Trauma and Emergency, University Malaya Medical Center, 59100 Kuala Lumpur, Malaysia.</aff>
<author-notes><corresp id="FNA_envelop">✉ Corresponding author: Ravi Chandra Vemuri, Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia. Email: <email>ravichandra@siswa.um.edu.my</email>
; <email>ravichandra1788@gmail.com</email>
. Prof. Dr. Shamala Devi Sekaran, Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia. Email: <email>shamala@um.edu.my</email>
; <email>shamalamy@yahoo.com</email>
</corresp>
<fn fn-type="conflict"><p>Competing Interest: Authors have declared that no competing interest exists.</p>
</fn>
</author-notes>
<pub-date pub-type="collection"><year>2015</year>
</pub-date>
<pub-date pub-type="epub"><day>5</day>
<month>5</month>
<year>2015</year>
</pub-date>
<volume>12</volume>
<issue>5</issue>
<fpage>387</fpage>
<lpage>396</lpage>
<history><date date-type="received"><day>22</day>
<month>9</month>
<year>2014</year>
</date>
<date date-type="accepted"><day>8</day>
<month>1</month>
<year>2015</year>
</date>
</history>
<permissions><copyright-statement>© 2015 Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions.</copyright-statement>
<copyright-year>2015</copyright-year>
</permissions>
<abstract><p><bold>Background</bold>
: Rosacea is a characteristic cutaneous disorder with a diverse clinical manifestations ranging from facial vascular hyper-reactivity to sebaceous gland hyperplasia. Many theories on pathophysiology of rosacea were proposed over the past decade, however the pathogenicity is poorly understood.</p>
<p><bold>Aim: </bold>
To review the evidence on different pathophysiological correlations of rosacea.</p>
<p><bold>Methods: </bold>
A literature search was conducted for studies published between 1990 to March 2014. The inclusion criteria was pathophysiology, randomized controlled trials, controlled trials on rosacea.</p>
<p><bold>Results: </bold>
Out of 5141 articles, 14 high quality studies met all the selection criteria. Of 14 articles, 5 are randomized control trials (RCTs), 2 are controlled trial, 3 comparative trials, 2 observational trials, 1 prospective and 1 diagnostic trial. The studies were categorized into two groups: the trigger factors and sub-types & symptoms. Of 7 high quality studies, 4 provided strong evidence that immune responses causing disease triggered by external/internal factors such as sunlight, food and chemical agents, 3 trials provided significant evidence of microorganisms as causative agents. The remaining trials did not provide significant evidences on pathophysiology.</p>
<p><bold>Conclusion: </bold>
Vasculature, chronic inflammatory responses, environmental triggers, food and chemicals ingested and microorganisms either alone or in combination are responsible for rosacea. Many promising drugs are under various phases of clinical trials and interestingly, probiotics could also possibly be used as one of the treatment option.</p>
</abstract>
<kwd-group><kwd>Rosacea</kwd>
<kwd>pathophysiology</kwd>
<kwd>vasculature</kwd>
<kwd>Chronic Inflammation</kwd>
<kwd>randomized control trials.</kwd>
</kwd-group>
</article-meta>
</front>
<floats-group><fig id="F1" position="float"><label>Figure 1</label>
<caption><p>Flow diagram for selection process.</p>
</caption>
<graphic xlink:href="ijmsv12p0387g001"></graphic>
</fig>
<fig id="F2" position="float"><label>Figure 2</label>
<caption><p>Mechanism of ROS resulting in inflammation <xref rid="B40" ref-type="bibr">40</xref>
-<xref rid="B43" ref-type="bibr">43</xref>
.</p>
</caption>
<graphic xlink:href="ijmsv12p0387g002"></graphic>
</fig>
<fig id="F3" position="float"><label>Figure 3</label>
<caption><p>The presumed pathophysiology of rosacea in correlation with specific molecular, immunological, neuronal and clinical triggers. (A) Recurrent exposure to extreme sunlight (environmental changes) causes the dermal matrix degeneration, which in turn may trigger genetic predisposition leading to hypersensitivity and flush on the skin. (B) As a part of hypersensitivity, it triggers the innate immune response. (C) Effect of microorganisms like Demodex and Helicobacter pylori gives rise to the several inflammatory responses in the body. (D) Chemical and food agents would also trigger inflammatory responses. (E) Vasodilation of blood vessels by immune responses that may lead to Telangiectasia, Erythema. (F) Neural activation results in vasodilatation, edema and burning sensation (G) Chronic neurogenic inflammation may lead to persistent erythema, followed by angiogenesis. (H) Imbalance in lymphatic system leads to lymphedema followed (I) Glandular hyperplasia and fibrosis (J) leading to inflammatory responses like vasodilation, extravasation and plasma leakage (severe case) giving rise to (K) erythema, edema and papules.</p>
</caption>
<graphic xlink:href="ijmsv12p0387g003"></graphic>
</fig>
<table-wrap id="T1" position="float"><label>Table 1</label>
<caption><p>Detailed description of trials</p>
</caption>
<table frame="hsides" rules="groups"><thead valign="top"><tr><th rowspan="1" colspan="1">Author</th>
<th rowspan="1" colspan="1">Trial type</th>
<th rowspan="1" colspan="1">Sample size & description</th>
<th rowspan="1" colspan="1">Length</th>
<th rowspan="1" colspan="1">Outcome/Result</th>
</tr>
</thead>
<tbody valign="top"><tr><td rowspan="1" colspan="1">Jarmuda et al<break></break>
(Ireland)<break></break>
<xref rid="B25" ref-type="bibr">25</xref>
</td>
<td rowspan="1" colspan="1">Controlled trial on Demodex levels on face of patients</td>
<td rowspan="1" colspan="1">n= 127, R= 75, HC= 52</td>
<td rowspan="1" colspan="1">15 weeks</td>
<td rowspan="1" colspan="1">Demodex ↑ in patients (P = 0.0001)</td>
</tr>
<tr><td rowspan="1" colspan="1">Sherif et al<break></break>
(Libya)<break></break>
<xref rid="B27" ref-type="bibr">27</xref>
</td>
<td rowspan="1" colspan="1">Randomized controlled trial on H. pylori</td>
<td rowspan="1" colspan="1">n= 36, Mean age ± SD = 37.8 ± 6.6 years</td>
<td rowspan="1" colspan="1">21 weeks</td>
<td rowspan="1" colspan="1">Sun exposure and H. Pylori have possibly have role in Rosacea. (<italic>P</italic>
= 0.005)</td>
</tr>
<tr><td rowspan="1" colspan="1">Brown et al<break></break>
(USA)<break></break>
<xref rid="B48" ref-type="bibr">48</xref>
</td>
<td rowspan="1" colspan="1">Comparative analysis (Rosacea (R) & Cutaneous Lupuserythematous (LE))</td>
<td rowspan="1" colspan="1">n= 57, R= 27; LE=30<break></break>
Average age=<break></break>
(55.5 vs 42.3 years<break></break>
<italic>P</italic>
= .0029)</td>
<td rowspan="1" colspan="1">6 months</td>
<td rowspan="1" colspan="1">T-Cell mediated responses have significant role in R and LE.</td>
</tr>
<tr><td rowspan="1" colspan="1">Tisma et al.<break></break>
(Croatia)<break></break>
<xref rid="B36" ref-type="bibr">36</xref>
</td>
<td rowspan="1" colspan="1">Randomized controlled trial on serum peroxides & ferritin levels</td>
<td rowspan="1" colspan="1">n= 71, R= 60; HC= 11<break></break>
Mean age= 30 to 70 years</td>
<td rowspan="1" colspan="1">6 months</td>
<td rowspan="1" colspan="1">Serum peroxides ↑ & serum total anti-oxidative potential levels ↓ in R v's HC (<italic>P</italic>
= .05)</td>
</tr>
<tr><td rowspan="1" colspan="1">Bakar et al.<break></break>
(Turkey)<break></break>
<xref rid="B39" ref-type="bibr">39</xref>
</td>
<td rowspan="1" colspan="1">Controlled trials on ROS levels</td>
<td rowspan="1" colspan="1">n= 42, R= 17, HC= 25<break></break>
Mean ± SD age 50.3 ±19, 15.1 years.</td>
<td rowspan="1" colspan="1">6 weeks</td>
<td rowspan="1" colspan="1">ROS levels ↑ in rosacea patients than in HC</td>
</tr>
<tr><td rowspan="1" colspan="1">Cribier et al.<break></break>
(France)<break></break>
<xref rid="B19" ref-type="bibr">19</xref>
</td>
<td rowspan="1" colspan="1">Diagnostic trial on Pathophysiology of Rosacea</td>
<td rowspan="1" colspan="1">n= 86<break></break>
mean age= 25 to 49 years</td>
<td rowspan="1" colspan="1">3 months</td>
<td rowspan="1" colspan="1">Vasculature and Inflammation primary factors in Rosacea</td>
</tr>
<tr><td rowspan="1" colspan="1">LE Heuzey et al.<break></break>
(France)<break></break>
<xref rid="B21" ref-type="bibr">21</xref>
</td>
<td rowspan="1" colspan="1">Randomized controlled trial on Amiodarone on skin (redness/flush)</td>
<td rowspan="1" colspan="1">n= 504, CI = 95%<break></break>
Middle-aged patients</td>
<td rowspan="1" colspan="1">12 months</td>
<td rowspan="1" colspan="1">HR = 0.80; 95%<break></break>
CI 0.60-1.07; P = 0.129<break></break>
Redness ↑</td>
</tr>
<tr><td rowspan="1" colspan="1">Tsiskarishvili<break></break>
et al.<break></break>
(Georgia)<break></break>
<xref rid="B49" ref-type="bibr">49</xref>
</td>
<td rowspan="1" colspan="1">Observational trial on early stage treatment</td>
<td rowspan="1" colspan="1">n= 50, R= 25, HC= 25,<break></break>
mean age= 25 to 49 years</td>
<td rowspan="1" colspan="1">12 months</td>
<td rowspan="1" colspan="1">Beta-blockers and Rozaliak<break></break>
effective for treatment</td>
</tr>
<tr><td rowspan="1" colspan="1">Tan J et al.<break></break>
(Germany)<break></break>
<xref rid="B46" ref-type="bibr">46</xref>
</td>
<td rowspan="1" colspan="1">Observational cross-sectional survey on clinical association &<break></break>
progression b/w sub-types</td>
<td rowspan="1" colspan="1">n (R) = 135</td>
<td rowspan="1" colspan="1">3 months</td>
<td rowspan="1" colspan="1">Disease progression amongst associated sub-types. (<italic>P</italic>
= 0.005)</td>
</tr>
<tr><td rowspan="1" colspan="1">Guzman-Sanchez<break></break>
et al.<break></break>
(USA)<break></break>
<xref rid="B18" ref-type="bibr">18</xref>
</td>
<td rowspan="1" colspan="1">Comparative trial to assess heat pain thresholds and skin blood flow</td>
<td rowspan="1" colspan="1">n= 24, R= 16;<break></break>
HC= 8</td>
<td rowspan="1" colspan="1">5 weeks</td>
<td rowspan="1" colspan="1">Enhanced sensitivity to<break></break>
noxious heat stimuli/blood<break></break>
flow in rosacea-affected skin.<break></break>
<italic>P </italic>
< .05.</td>
</tr>
<tr><td rowspan="1" colspan="1">Casas et al.<break></break>
(France)<break></break>
<xref rid="B24" ref-type="bibr">24</xref>
</td>
<td rowspan="1" colspan="1">Prospective/multicenter trial on Demodex, Rosacea & immune responses.</td>
<td rowspan="1" colspan="1">n= 98, R= 50<break></break>
HC= 48</td>
<td rowspan="1" colspan="1">12 months</td>
<td rowspan="1" colspan="1">D. folliculorum density was<break></break>
5.7 times ↑ in rosacea patients<break></break>
than in healthy volunteers.<break></break>
<italic>P</italic>
< 0.05.</td>
</tr>
<tr><td rowspan="1" colspan="1">Smith et al.<break></break>
(USA)<break></break>
<xref rid="B50" ref-type="bibr">50</xref>
</td>
<td rowspan="1" colspan="1">Controlled trial on vascular endothelial receptor (VEGF) expression in rosacea</td>
<td rowspan="1" colspan="1">n= 20 (R)<break></break>
Mean age= 25 - 35 years</td>
<td rowspan="1" colspan="1">4 weeks</td>
<td rowspan="1" colspan="1">VEGF-ligand binding in rosacea could contribute<break></break>
vascular & cellular changes</td>
</tr>
<tr><td rowspan="1" colspan="1">Coda et al.<break></break>
(USA, U.K)<break></break>
<xref rid="B32" ref-type="bibr">32</xref>
</td>
<td rowspan="1" colspan="1">Randomized multicenter on role of cathelicidin in rosacea</td>
<td rowspan="1" colspan="1">n= 60 (R= 55)<break></break>
HC= 5<break></break>
age= 18-40 years</td>
<td rowspan="1" colspan="1">16 weeks</td>
<td rowspan="1" colspan="1">Cathelicidin ↑ & serine protease activity ↑ in rosacea patients.</td>
</tr>
<tr><td rowspan="1" colspan="1">Parodi et al.<break></break>
(Italy)<break></break>
<xref rid="B66" ref-type="bibr">66</xref>
</td>
<td rowspan="1" colspan="1">Randomized Controlled trial on gut bacteria</td>
<td rowspan="1" colspan="1">n= 113 (R= 53), mean age, 52 ± 15 years.<break></break>
HC= 60 mean age, 49 ± 11 years; 82 women, 31 men.</td>
<td rowspan="1" colspan="1">9 months</td>
<td rowspan="1" colspan="1">Gut bacteria ↑ in rosacea patients when compared to HCs. Rifaximin drug therapy was given to rosacea patients and disease ↓</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn><p><bold>N= </bold>
Total number of patients; <bold>R</bold>
= Rosacea; <bold>HC</bold>
= Healthy control; <bold>HR</bold>
= hazard ratio; <bold>P= </bold>
Significance; <bold>CI</bold>
= confidence interval; ↑ = High; ↓ = Low.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="T2" position="float"><label>Table 2</label>
<caption><p>List of drugs under trials</p>
</caption>
<table frame="hsides" rules="groups"><thead valign="top"><tr><th rowspan="1" colspan="1">Type</th>
<th rowspan="1" colspan="1">Investigational Drug</th>
<th rowspan="1" colspan="1">Intended Actions</th>
<th rowspan="1" colspan="1">Clinical trial phase</th>
<th rowspan="1" colspan="1">Dosage form</th>
<th rowspan="1" colspan="1">References</th>
</tr>
</thead>
<tbody valign="top"><tr><td rowspan="1" colspan="1">Erythematotelangiectatic rosacea</td>
<td rowspan="1" colspan="1">Laropiprant</td>
<td rowspan="1" colspan="1">Human prostaglandin D2 receptor-1</td>
<td rowspan="1" colspan="1">Early phase</td>
<td rowspan="1" colspan="1">Topical</td>
<td rowspan="1" colspan="1"><xref rid="B52" ref-type="bibr">52</xref>
</td>
</tr>
<tr><td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1">(On hold)</td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1">Aganirsen</td>
<td rowspan="1" colspan="1">Antisense oligonucleotide</td>
<td rowspan="1" colspan="1">Early phase</td>
<td rowspan="1" colspan="1">Topical</td>
<td rowspan="1" colspan="1"><xref rid="B53" ref-type="bibr">53</xref>
</td>
</tr>
<tr><td rowspan="1" colspan="1">Papulopustular rosacea</td>
<td rowspan="1" colspan="1">Omiganan pentahydrochloride</td>
<td rowspan="1" colspan="1">Disruption of the cytoplasmic membranes</td>
<td rowspan="1" colspan="1">Phase III</td>
<td rowspan="1" colspan="1">Topical</td>
<td rowspan="1" colspan="1"><xref rid="B60" ref-type="bibr">60</xref>
, <xref rid="B61" ref-type="bibr">61</xref>
</td>
</tr>
<tr><td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1">Ivermectin 1% cream</td>
<td rowspan="1" colspan="1">-n/a-</td>
<td rowspan="1" colspan="1">Phase III completed</td>
<td rowspan="1" colspan="1">Topical</td>
<td rowspan="1" colspan="1"><xref rid="B55" ref-type="bibr">55</xref>
</td>
</tr>
<tr><td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1">Carbamide peroxide</td>
<td rowspan="1" colspan="1">Inhibiting inflammatory mediators</td>
<td rowspan="1" colspan="1">Phase III completed</td>
<td rowspan="1" colspan="1">Topical</td>
<td rowspan="1" colspan="1"><xref rid="B62" ref-type="bibr">62</xref>
</td>
</tr>
<tr><td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1">SGT-VD-54</td>
<td rowspan="1" colspan="1">-n/a-</td>
<td rowspan="1" colspan="1">Phase II</td>
<td rowspan="1" colspan="1">Topical</td>
<td rowspan="1" colspan="1"><xref rid="B62" ref-type="bibr">62</xref>
</td>
</tr>
<tr><td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1">Sarecycline hydrochloride</td>
<td rowspan="1" colspan="1">Down regulates inflammatory cytokine production</td>
<td rowspan="1" colspan="1">Phase II</td>
<td rowspan="1" colspan="1">Oral</td>
<td rowspan="1" colspan="1"><xref rid="B63" ref-type="bibr">63</xref>
</td>
</tr>
<tr><td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1">Apremilast</td>
<td rowspan="1" colspan="1">Modulates multiple anti-inflammatory pathways</td>
<td rowspan="1" colspan="1">Phase II completed</td>
<td rowspan="1" colspan="1">Oral</td>
<td rowspan="1" colspan="1"><xref rid="B56" ref-type="bibr">56</xref>
</td>
</tr>
<tr><td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1">Azelaic acid foam</td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1">Phase III ongoing</td>
<td rowspan="1" colspan="1">Topical Author et. al</td>
<td rowspan="1" colspan="1"><xref rid="B57" ref-type="bibr">57</xref>
</td>
</tr>
<tr><td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1">Incobotulinumtoxin A</td>
<td rowspan="1" colspan="1">-n/a-</td>
<td rowspan="1" colspan="1">Phase II</td>
<td rowspan="1" colspan="1">I.V</td>
<td rowspan="1" colspan="1"><xref rid="B58" ref-type="bibr">58</xref>
, <xref rid="B64" ref-type="bibr">64</xref>
</td>
</tr>
<tr><td rowspan="1" colspan="1">Phymatous Rosacea</td>
<td rowspan="1" colspan="1">No specific drug under trials</td>
<td rowspan="1" colspan="1">-n/a</td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td rowspan="1" colspan="1">Ocular Rosacea</td>
<td rowspan="1" colspan="1">No specific drug under trials</td>
<td rowspan="1" colspan="1">-n/a-</td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn><p>-n/a- = Not available; I.V= Intravenous.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</floats-group>
</pmc>
<affiliations><list><country><li>Malaisie</li>
</country>
</list>
<tree><country name="Malaisie"><noRegion><name sortKey="Vemuri, Ravi Chandra" sort="Vemuri, Ravi Chandra" uniqKey="Vemuri R" first="Ravi Chandra" last="Vemuri">Ravi Chandra Vemuri</name>
</noRegion>
<name sortKey="Gundamaraju, Rohit" sort="Gundamaraju, Rohit" uniqKey="Gundamaraju R" first="Rohit" last="Gundamaraju">Rohit Gundamaraju</name>
<name sortKey="Manikam, Rishya" sort="Manikam, Rishya" uniqKey="Manikam R" first="Rishya" last="Manikam">Rishya Manikam</name>
<name sortKey="Sekaran, Shamala Devi" sort="Sekaran, Shamala Devi" uniqKey="Sekaran S" first="Shamala Devi" last="Sekaran">Shamala Devi Sekaran</name>
</country>
</tree>
</affiliations>
</record>
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