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\def\RunningAuthor{Hemalatha C N et al.}
\firstPage{1552}
\articleType{Review Article}
\receivedDate{28 Feb 2021}
\acceptedDate{05 Apr 2021}
\revisedDate{30 Mar 2021}
\journalVolume{2021, 12}
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\journalDoi{ijrps.v12i2.4739}
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\title{A Review Study on Cellulitis}
\author{Hemalatha~C~N\textsuperscript{*}\textsuperscript{1},  
            Jagadeesan~B\textsuperscript{2},  
            Janani~N\textsuperscript{1},  
            Aniesh~Kumar~A\textsuperscript{1},  
            Harinathan~R\textsuperscript{1}, 
            Harikrishnan~N\textsuperscript{1}~\\[5pt]{\textsuperscript{1}Faculty of Pharmacy, Dr.M.G. R Educational and Research Institute, Velappanchavadi, Chennai, Tamil Nadu, India}~\\{\textsuperscript{2}Faculty of Pharmacy, Sri Ramachandra Institute of Higher Education and Research  (SRIHER), Porur, Chennai, Tamil Nadu, India}}

\begin{abstract}
Cellulitis is a clinical condition which is characterised by reddishness, soreness, localized pain, erythema, swelling and formation of abscess in the leg, pyrexia and an increase in the heartbeat. It is the infection of the sub-cutaneous tissue and dermal layer usually found complicating a wound or ulcer. It is considered an infectious disease as it causes morbidity and mortality. It is also called skin diseases, as the skin is involved and lacks sharp demarcation from uninvolved skin. Cellulitis spreads rapidly and is pyogenic in nature and is frequently associated with lymphangitis and fever. \textit{Streptococci} (\textit{streptococci pyogenes) and staphylococcus aureus }are the two species which causes cellulitis. Five types of cellulitis can be classified they are facial cellulitis, periorbital cellulitis, breast cellulitis, perianal cellulitis. Diagnosis of cellulitis is based on morphological features of the lesion and a CT scan is required for determining cellulitis. By the visual inspection, the cellulitis is spotted. The common risk factor for cellulitis is oedema. If the cellulitis patient has Diabetes Mellitus or injury in the skin or any inflammation in the liver, they are considered to be in a dangerous state. Non-Steroidal Anti-Inflammatory Drugs are prescribed to decrease the clinical features. Clindamycin, Dicloxacillin are antibiotics that are administered to cure cellulitis. This review discusses the general information regarding cellulitis, its clinical indications, pathophysiology, microbiology and its treatment. 
\end{abstract}\def\keywordstitle{Keywords}

\begin{keywords}Cellulitis,\newline streptococci aureus,\newline CT scan,\newline Non {\textendash} Steroidal Anti-Inflammatory Drugs,\newline Clindamycin,\newline Dicloxacillin
\end{keywords}
\twocolumn[ \maketitle {\printKwdAbsBox}]
\makeatletter{\raggedright\textsuperscript{*}Corresponding Author\par Name:\ Hemalatha~C~N~\\ Phone:\ 9003843867~\\  Email:\ hemalatha.pharm@drmgrdu.ac.in 
        \par}\vspace*{-11pt}\hrulefill\par{\fontsize{12}{14}\selectfont ISSN: 0975-7538}\par% 
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\section{ Introduction}
Cellulitis is defined as the acute infection of the sub-cutaneous tissue and dermal layer. It is an infectious disease which is responsible for unwholesomeness (morbidity) and loss of life (mortality). It is a micro-organism infection where the skin is concerned. It is considered as an epidemic disease which affects both adults and children. Cellulitis can be classified into five types\unskip~\citep{1076857:22011000}.

Cellulitis occurs due to two species. They are \textit{Streptococci (streptococcus pyogenes) } and \textit{Staphylococcus aureus}. In that,\textit{} the most identified cause is \textit{Staphylococcus aureus}.\textit{\space } Cellulitis requires hospitalization in extreme condition. Computed Tomography (CT) scanning is used in determining cellulitis. However, X-rays are not required in most cases, but in some cases, it is needed\unskip~\citep{1076857:22010999}.

Moreover, people's caution in cleanliness and their knowledge in vaccine progression had a phenomenal decline in the disease's cellulitis. Non- Steroidal 


\begin{table*}[!htbp]
\caption{\boldmath {The Types of Cellulitis} }
\label{tw-1fb25b31dcd6}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.2776\linewidth-2\tabcolsep}p{\dimexpr.7224\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Types & Description\\
\tblmidrule 
Facial cellulitis &
  If there is any inflammation like an ache, swellings, reddishness on the face, lips, tongues, then the person is having more chance to acquire the clinical condition called cellulitis.\\
Periorbital cellulitis &
  It is also named preseptal cellulitis. In this case, the person may have the chances to be getting affected in the eye, eyelids or every side of the eye's skin.\\
Orbital cellulitis &
  It is a severe condition, where the Medical Practioner consultation is very must as it has a bigger chance of the brain getting infected.\\
Breast cellulitis &
  In this case, the body part of the breast is being affected. In this case, female patients are getting affected.\\
Perianal cellulitis &
  In this type, the perianal cellulitis is mostly noticed in males. \mbox{}\protect\newline In this type, every side of the anus's skin will be looked bright red in colour.\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Steroidal Anti-Inflammatory drugs and Anti-Bacterial drugs to treat Cellulitis} }
\label{tw-813543b12bbf}
\def\arraystretch{1.1}
\ignorespaces 
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\begin{tabulary}{\linewidth}{p{\dimexpr.2388\linewidth-2\tabcolsep}p{\dimexpr.4028\linewidth-2\tabcolsep}p{\dimexpr.17589999999999996\linewidth-2\tabcolsep}p{\dimexpr.1825\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Drugs Name & Uses & Dosage & Strength\\
\tblmidrule 
Dicloxacillin, \mbox{}\protect\newline Amoxicillin &
  Used in cellulitis's initial stages &
  Capsule &
  250mg,500mg\\
Clindamycin  &
  Used as a substitute to patient's, those who are having an allergic reaction to drug ``Penicillin." &
  Capsule &
  150mg,300mg\\
Levofloxacin or \mbox{}\protect\newline Fluoroquinolones  &
  As alternative medicine &
  Tablet &
  250mg,500mg,750mg\\
Parenteral antibiotic \mbox{}\protect\newline (Cefazolin) &
  Medical practitioners prefer this as initial dose. &
  Injection &
  1g/100ml\\
Ibuprofen &
  Prescribed for reducing the body's temperature as well as ache. &
  Tablet &
  600mg/1\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}
Anti-inflammatory Drugs (NSAID'S) are administered to reduce the inflammation signs, but the bacteria are proliferated as a side effect of Non-Steroidal Anti-inflammatory Drugs (NSAID'S). Anti-bacterial drugs such as Dicloxacillin, Clindamycin, and Levofloxacin are prescribed to cure cellulitis. Superficial cellulitis, which involves lymphatic activity known as Erysipelas, does have an indurated, raised border that demarcates it from normal skin. These distinctive features create a ``peau d'orange'' appearance\unskip~\citep{1076857:22011002}.

\textbf{Types of Cellulitis}

Cellulitis is of different types depending on where the infection occurs. They are five types of cellulitis (Table~\ref{tw-1fb25b31dcd6}) such as facial cellulitis, periorbital cellulitis, orbital cellulitis breast cellulitis and perianal cellulitis\unskip~\citep{1076857:22011001}.

\textbf{Clinical indications\ensuremath{^{}}}

The clinical features are discussed below

\textbf{First line features}


  
  \begin{enumerate}
  \item \relax Reddishness
  \item \relax Ache
  \item \relax Soreness
  \item \relax Swellings
  \end{enumerate}
  \textbf{Clinical indicators}


  
  \begin{enumerate}
  \item \relax Formation of abscess in the leg
  \item \relax Pyrexia
  \item \relax Chillness
  \item \relax Increasing heartbeat
  \item \relax Head pain
  \item \relax Reduction in the blood pressure level \unskip~\citep{1076857:22011008}.
  \end{enumerate}
  
\begingroup
\makeatletter\if@twocolumn\@ifundefined{theposttbl}{\gdef\TwoColDocument{true}\onecolumn\onecolumn}{}\fi\makeatother \setlength\LTcapwidth{\textwidth}
\begin{longtable}{p{\dimexpr.10419999999999998\linewidth-2\tabcolsep}p{\dimexpr.1066\linewidth-2\tabcolsep}p{\dimexpr.1132\linewidth-2\tabcolsep}p{\dimexpr.10099999999999998\linewidth-2\tabcolsep}p{\dimexpr.11430000000000003\linewidth-2\tabcolsep}p{\dimexpr.09750000000000004\linewidth-2\tabcolsep}p{\dimexpr.18750000000000004\linewidth-2\tabcolsep}p{\dimexpr.1757\linewidth-2\tabcolsep}}
\caption{\boldmath {Drug Interactions and Toxicity} }
\label{tw-b150bc55f7af}
\def\arraystretch{1.1}\\\endfirsthead \hline \noalign{\vskip3pt} \noalign{\textit{Table \thetable\ continued}} \noalign{\vskip3pt} \hline \endhead \hline \noalign{\vskip3pt} \noalign{\textit{\hfill Continued on next page}} \noalign{\vskip3pt} \endfoot \endlastfoot 
\tbltoprule \rowcolor{kwdboxcolor}Chemical Name & Molecular Weight & Metab \mbox{}\protect\newline olism & Excretion & Generic Name and Brand Name & t\ensuremath{_{1/2}} & Drug  \mbox{}\protect\newline Interactions & Toxicity\\
\tblmidrule 
Diclox \mbox{}\protect\newline acillin &
  470.327 g/mol  &
  In liver &
  Excreted in  \mbox{}\protect\newline Renal and  \mbox{}\protect\newline Biliary &
  Diclox \mbox{}\protect\newline acillin   \mbox{}\protect\newline (Dynapen)  &
  0.7 hours  &
  It has possible interactions with the below given drugs \mbox{}\protect\newline 1. Methotrexate \mbox{}\protect\newline 2. Warfarin \mbox{}\protect\newline 3. Tetracycline &
  Irritation, rash, laboured breathing, hives, itching and wheezing, nausea and chills, as well as fever are the symptoms of overexposure. \\
Amoxi \mbox{}\protect\newline cillin &
  365.40 g/mol  &
  In liver &
  Excreted in Kidney &
  Amoxi \mbox{}\protect\newline cillin \mbox{}\protect\newline (Amoxil) &
  1hour 1min  \mbox{}\protect\newline 3 sec &
  Amoxicillin may interact with the following drugs, \mbox{}\protect\newline  Methotrexate, Warfarin, Dabigatran, Uricosuric drug.  \mbox{}\protect\newline Oral contraceptives may become less effective.   \mbox{}\protect\newline Typhoid vaccine  \mbox{}\protect\newline  &
  Nausea, vomiting, diarrhoea and abdominal pain. Acute oliguric renal failure and haematuria may occur following large doses. \\
Clinda \mbox{}\protect\newline mycin &
  424.981 g/mol  &
  In liver &
  Excreted in Biliary and Renal &
  Clinda \mbox{}\protect\newline mycin  \mbox{}\protect\newline (Cleocin)  &
  2-3hours &
  It may have prolong   \mbox{}\protect\newline effects of neuromuscular-blocking drugs with succinylcholine and   \mbox{}\protect\newline vecuronium  &
  Adverse effects of the drugs are nausea may be dose-limiting diarrhoea, allergic reaction, pseudomembranous colitis, transient neutropenia and hepatoxicity, agranulocytosis as well as eosinophilia.  \\
Clarith romycin &
  747.964 g/mol &
  In liver \mbox{}\protect\newline  &
  Excreted in Urine &
  Clarith  \mbox{}\protect\newline romycin (Biaxin)  &
  3-4 hours &
  Clarithromycin inhibits a liver enzyme, CYP3A4  &
  Diarrhoea, dyspepsia and abnormal taste, abdominal discomfort, as well as nausea.   \mbox{}\protect\newline Transient hearing loss with high doses has been observed. \\
Azithr \mbox{}\protect\newline omycin &
  748.996 g/mol  &
  In liver &
  Excreted in Biliary and Renal &
  Azithr \mbox{}\protect\newline omycin \mbox{}\protect\newline (Zithromax) &
  11{\textendash}14 hours (single dose) 68 hours (multiple dosing) &
  This drug may interact with  \mbox{}\protect\newline (R)-warfarin  \mbox{}\protect\newline (S)-Warfarin  \mbox{}\protect\newline 6-O-benzyl \mbox{}\protect\newline guanine  \mbox{}\protect\newline 4-hydroxy \mbox{}\protect\newline coumarin  \mbox{}\protect\newline 7-ethyl-10-hydroxyca \mbox{}\protect\newline mptothecin  \mbox{}\protect\newline 5-androst \mbox{}\protect\newline enedione  \mbox{}\protect\newline 7-Deaza \mbox{}\protect\newline guanine  \mbox{}\protect\newline 3,5-diiodothy \mbox{}\protect\newline ropropionic acid  \mbox{}\protect\newline 6-O-benzy \mbox{}\protect\newline lguanine  &
  The major adverse effects of the Azithromycin are hearing loss and cardiovascular arrhythmias. \\
Cepha \mbox{}\protect\newline lexin &
  347.389 g/mol  &
  80\% gets excrete and unchanged in urine within 6 hours of administration &
  Excreted in renal &
  Cepha \mbox{}\protect\newline lexin \mbox{}\protect\newline (Keflex) &
  0.6-1.2 hours &
  Renal excretion of cefalexin is delayed by probenecid also interacts with metformin hydrochloride. &
  Symptoms of high dose include Haematuria, diarrhoea, nausea and upper abdominal pain, as well as vomiting. \\
Levof \mbox{}\protect\newline loxacin &
  361.373 g/mol  &
  Dimethyl and N-oxides gets metabolite &
  Excreted in renal &
  Levof \mbox{}\protect\newline loxacin \mbox{}\protect\newline (Levaquin) &
  6.9 hours &
  This drug interacts with  \mbox{}\protect\newline (R)-warfarin  \mbox{}\protect\newline (S)-Warfarin  \mbox{}\protect\newline 4-hydroxy \mbox{}\protect\newline coumarin  \mbox{}\protect\newline 5-androste \mbox{}\protect\newline nedione  \mbox{}\protect\newline 6-O-benzylg \mbox{}\protect\newline uanine  \mbox{}\protect\newline 7-ethyl-10-hydroxyca \mbox{}\protect\newline mptothecin  &
  The adverse of the drug Levofloxacin are drowsiness, Dysarthria, dizziness, hot and cold flashes, swelling and numbness in the face, nausea, and also disorientation. \\
\tblbottomrule 
\end{longtable}
\endgroup
\makeatletter\@ifundefined{TwoColDocument}{}{\twocolumn}\makeatother 
\textbf{Pathophysiology}


  
  \begin{enumerate}
  \item \relax Cellulitis is an infection of the subcutaneous tissue and dermal layer. It happens in the skin by the entry of pathogens into the dermis skin's layer.
  \item \relax The phalanges webspace bacteria, fungal, foot infections pressure ulcers and venous leg ulcers these things cause the cutaneous barrier disruption.
  \item \relax The lowest level surface pH, low point temperature and commensal micro-organisms availability decrease the skin external pathogenic organism's expansion\unskip~\citep{1076857:22011003}.
  \end{enumerate}
  In cellulitis,


  
  \begin{enumerate}
  \item \relax Swelling in the inner layer of skin
  \item \relax Lymphatic dilation
  \item \relax Dispersed huge impartial filtration on every side of the bloodvessel\unskip~\citep{1076857:22010994}.
  \end{enumerate}
  The above-mentioned characteristics are the cytological characteristics of cellulitis. In the next step, the lymphocytes, as well as histocytes, also incorporates as its biological characters. Commonly the unfavourable conclusion is because of the cultures performed with needle aspiration or biopsy. When the bacteria's concentration is in a short amount, it gives favourable outcomes. This study indicates that a very low number of bacteria are accountable for the inauguration of sturdy provocative reaction\unskip~\citep{1076857:22010993}.

\textbf{Microbiology\ensuremath{^{}}}

In adults, cellulitis occurs due to two species. They are as follows,


  
  \begin{enumerate}
  \item \relax Streptococci (streptococcus pyogenes)
  \item \relax Staphylococcus aureus 
  \end{enumerate}
  In a review by \unskip~\cite{1076857:22011012} in the year 2016, 1000 adults and children patients in the United States of America (USA) had undergone needle aspiration or punch biopsy.\ensuremath{^{}} 16\% of them had civilizations that established a bacterial diagnosis.\ensuremath{^{}} And in a favourable conclusion, it is identified that 5\% were \textit{Staphylococcus aureus} and 27\% were \textit{streptococcus pyogenes. } Bacteria like Haemophilus influenza may cause cellulitis and it causes facial cellulitis in young children\unskip~\citep{1076857:22011005}.

\textbf{Risk Factor's For Cellulitis }

Edema is considered as the not uncommon risk factor for cellulitis. The lymphedema is the specific risk factor since bacterial growth is aided by the lymphatic fluid.\ensuremath{^{}} Fluid is supposed to facilitate bacterial growth\unskip~\citep{1076857:22011012}.

The patient is at risk or dangerous state if they have the following,

1. Diabetes mellitus

2. Injury in the skin

3. Inflammation in the liver (Hepatitis)

4. Circulatory complications like not enough blood flow to the arms and legs, poor drainage of veins


  
  \begin{enumerate}
  \item \relax Dermatological issues like eczema, psoriasis, which may lead to chickenpox\unskip~\citep{1076857:22010996}.
  \end{enumerate}
  5. Dermatological issues like eczema, psoriasis, which may lead to chickenpox\unskip~\citep{1076857:22010996}.

\textbf{Identification of Cellulitis}\ensuremath{^{}}

There are no diamond calibre approaches to identify cellulitis\unskip~\citep{1076857:22011007}.


  
  \begin{enumerate}
  \item \relax It is detected based on the corporal (physical) check-up and the patient's previous medical records.
  \item \relax Computed Tomography (CT) scans as well as ultrasound is used to discover deeper infections like abscesses.
  \item \relax Additionally, a blood test is required if the medical officer suspects that it may spread to your blood.
  \item \relax X-rays are needed if a foreign particle present in the skin or behind the bone.
  \item \relax Moreover, it is spotted by visual inspection too.
  \item \relax In cellulitis, Pastecurella multicoida is combined with animal bites, maximum in cat bites\unskip~\citep{1076857:22011010}.
  \end{enumerate}
  \textbf{Treatment}\ensuremath{^{}}

Antibiotics are prescribed to cure cellulitis. It is administered orally for most of the patients. Hospitalization is required for extreme stages of cellulitis. During hospitalization, the antibiotics are administered in the intravenous IV route\unskip~\citep{1076857:22011004}.

In some cases, the antibiotics are prescribed for many weeks and even months, this is followed only if the patients often suffer from severe cellulitis, if not, antibiotics are prescribed only for a limited duration. Also, Non-Steroidal Anti-Inflammatory Drugs are prescribed to treat cellulitis\unskip~\citep{1076857:22010997}.

\textbf{Drugs Used in Cellulitis }

The Non {\textendash} Steroidal Anti-Inflammatory Drugs and Anti-bacterial drugs are administered to treat cellulitis and this is discussed briefly in the Table~\ref{tw-813543b12bbf}. Beta-lactam antibiotics having activity against penicillinase-producing \textit{S. aureus} are the drugs of choice. Cefazolin (first generation cephalosporin), nafcillin (synthetic penicillin) and ceftriaxone (third-generation cephalosporin) are initial treatment options for cellulitis\unskip~\citep{1076857:22011011}.

If the patient is suspected to have methicillin-resistant S. aureus (MRSA) or is highly allergic to penicillin, then linezolid and vancomycin can be treated for cellulitis. IV should be given as an initial treatment in the hospital if the inflammation is spreading very rapidly or if the patient has a significant systemic response such as chills and fever or occurrence of any complicating conditions like neutropenia, cardiac failure, immuno suppression, or renal insufficiency\unskip~\citep{1076857:22011009}. Structures, Molecular weight, Metabolism, Excretion, Generic name and Brand Name half- life period (t\ensuremath{_{1/2}}), Drug interactions and toxicity of the drugs are discussed in Table~\ref{tw-b150bc55f7af}.

\textbf{Preventive Measures}
  
  \begin{enumerate}
  \item \relax As there is a famous proverb, ``cleanliness is next to godliness'' here, in this cellulitis condition, cleanliness will prevent the cellulitis infection.
  \item \relax Maintaining good hygiene like washing hands properly will be the best preventive measure.
  \item \relax If the person has dry skin, he/she is advised to intake plenty of water.
  \item \relax Also, applying lotion or ointment to the braked skin will be an effective preventive measure.
  \item \relax It is advised to have the avoidance antibiotic, which is prescribed by your Medical officer\unskip~\citep{1076857:22010995}.
  \end{enumerate}
  
    
\section{\textbf{Discussion }\ensuremath{^{}}}
Majority of the patients who are affected with cellulitis gets a quick response to the antibiotics. In unusual cases, the cellulitis may reach the systemic circulation and it becomes complicated. In some rare cases, surgery is needed to clear the abscess, also to detach the deceased tissue\unskip~\citep{1076857:22011006}.
    
\section{Conclusions}
Cellulitis is an infectious clinical condition where micro-organism is concerned. It is an antibacterial skin disease where it has to be treated effectively at the early stage. Cellulitis is considered a general global issue and it could be reduced by curing its risk factor. Various information about Cellulitis has been discussed in this article and it can be treated with prior knowledge, even with low-cost antibiotics.
    
\section{ Acknowledgements}
The authors are thankful to the Faculty of Pharmacy and thankful to the management of Dr MGR Educational and Research Institute for providing this opportunity.

\textbf{Conflict of Interest}

The authors declare that they have no conflict of interest.

\textbf{Funding Support}

The authors declare that they have no funding support for this study.
    

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