حسام أبو عوض. 1 P a g e

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1 2 حسام أبو عوض P a g e

2 For the remaining of the MSS (microbiology) we will be discussing types of lesions and microorganisms and diseases related to them. Vesicles A vesicle may have begun as a macule/papule and it may turn (from a vesicle) to a bulla, may get infected and crust or may turn to a scar/ulcer. 90% of vesicular rashes are caused by viruses, namely herpesviridae. Rarely do you come across emergencies in dermatology,but today we are going to see two very serious dermatological conditions. Eczema Herpeticum Typically, the herpes simplex virus (HSV) causes (on a dermatological level) pharyngitis and gingivostomatitis (often in children and young adults). Most viral infections show flu-like symptoms (fever, malaise (tiredness), maybe chills, etc.). The HSV (in addition to the flu-like symptoms) is associated with difficulty in chewing and cervical lymphadenopathy. Note the large number of vesicles in pharyngitis [this characteristic allows us to differentiate it from normal occurrences like simple acne (small numberof vesicles)]. 2 P a g e

3 With HSV you expect to see ulcers/exudative lesions on the posterior pharynx and/or the tongue, the buccal mucosa and the gums (any combination). All of the above is not serious, in fact it s self-limiting so what does this have to do with the extremely dangerous condition noted in the subtitle (Eczema herpeticum) Well, it s true that the HSV infection is a simple disease, but that is only for those with no other underlying dermatological conditions! Patients with other dermatological conditions [occurs mostly with atopic dermatitis (AD)] get critically ill if they are infected with HSV (or other viruses) now this disease combination is called eczema herpeticum. Eczema herpeticum, which is a form of Kaposi varicelliform (a group of diseases in which cutaneous eruptions caused by certain viruses, including HSV, occurs), is an aggressive (and widely spread) form of vesicular eruptions. By itself, eczema herpeticum is not that serious, but, since a large area of the skin is affected, there is a high chance of bacterial superinfection (and bacteraemia) via the erupted vesicles and it is these superinfections that can lead to death [a large surface area of the skin is disrupted increasing the bio-burden (discussed in the previous lecture) and eventually the immune system won t be able to handle all the bio-burden from the bacteria and the viruses). Eczema herpeticum (and skin eruptions in general) is contagious, so it is important to inform the patient and keep them away from others. Children with AD have a much higher risk of eczema herpeticum and this is most commonly caused by HSV-1. In this image this patient (having eczema herpeticum) came with some vesicles to the clinic and they were sent back home with a diagnosis of Impetigo (a self-limiting skin infection), then they came back a few days later with the symptoms seen in the image. Not all eczema herpeticum cases are severe, sometimes the erupted vesicles 3 P a g e

4 are not widely spread over the skin lowering the risks associated with the disease [in all cases, whether severe or not, there will always be a viremia (virus in the blood) which is what leads to the flu-like symptoms]. Due to the medical emergency associated with eczema herpeticum, many diagnostic methods were developed for this disease. As usual, you must begin by taking the patient s history to see if they have/had atopic dermatitis (or other dermatological conditions). Take a sample from the erupted vesicles and send it to the lab; you can ask for PCR (especially in old, few numbered and atypical vesicles/viral particles), direct fluorescent antibody testing (usually rapid and accurate; 4-6h, differentiates between HSV-1 and HSV-2 infections) viral culture (accurate but slow ~ 2 days), immunohistochemistry (staining with antibodies) or even sending it to the pathology lab to note the viral cytopathic changes to the epithelium and the follicular epithelium (H&E stain). All these tests tell us whether the infection is viral (symptoms of viremia are supposed to be seen) or not(and also whether a bacterial infection is present). Tzanck-smear is a special diagnostic test that can be done by the physician in the clinic, so valuable that it is still used. A sample of the fluid inside the vesicles is taken (use a blade to open them), smeared, stained (Wright or Giemsa stain) and seen under a light microscope. This stain stains a special type of keratinocytes(a huge multinucleated keratinocyte characteristic for viral infections).however, this technique is very user dependent and requires a lot of skill and experience which is why we are progressing towards molecular techniques just send the sample and you ll get the result from the lab Treatment: Systemic anti-viral agents (acyclovir is preferred) if the patient was healthy (immunocompetent) you can give them a high dose (5 times per day) of oral anti-viral agents for a long time (7-10 days), but if they were immunocompromised you must inject the drugintra-venously. 4 P a g e

5 Foscarnet: rarely used (last-choice).it is active againstherpesviridae viruses. Not used normally due to its dangerous side effect of nephrotoxicity (50% of the patients), but when the patient might die from the disease then the risk is worth-taking Valacyclovir: this anti-viral can be used against herpesviridae viruses and needs a lower dosage than acyclovir, however, it is more expensive. Trifluridine and Vidarabine: Used topically if there is an ophthalmic (eye) involvement in the infection (consult an ophthalmologist immediately if you suspect an ophthalmic involvement). Antibiotics: in case of bacterial super-infection. Erythema Multiforme The other medical emergency in dermatology. Can be divided to erythema minor and erythema major. Begins as (vesicles then)blisters(erythema minor) and then progresses to more severe conditions (same as eczema herpeticum) like Steven- Johnson s syndrome (SJS) or Toxic epidermolysis necrosis (TEN) (erythema major). [It is now being debated that erythema multiforme is a completely separate disease from SJS and TEN]. Erythema Minor Erythema multiforme begins as vesicles, you can tell there is some detachment from the dermis, and progress to blisters with target lesions (see diagram).up to here the disease is usually self-limiting so the treatment is supportive (pain management, fever management, etc. no real treatment) and usually the attacks are acute so symptoms (flu like) are kinda aggressive. At times, the disease is recurring usually due to hypersensitivity reactions against certain infections (mostly HSV-1) or medications [antibiotics, antiepileptics (also SJS), sulfa drugs, penicillins, ciprofloxacin, etc.] so you could say that this is an abnormal behaviour of the body in response to HSV. 5 P a g e

6 It is seen in adults years old and rash isnoted 5-10 days after the onset of the viral infection (patient history: flu-like symptoms a week ago, some rash, etc.). Urticaria (the target lesions here) is the main diagnostic feature of the disease and you expect (in the patient s history) an allergythat was triggered and lesions later seen.in normal allergic attacks, within 24 hours of the removal of the allergen the lesions disappear, but in erythema multiforme it does not disappear after 24h, so the cause of this disease is said to be idiopathic (unknown, we didn t discover it yet). (microorganisms associated with the disease: HSV1 > 50%, others: mycoplasma, varicella, CMV, HIV). Treatment: Remove the allergen, give a supportive treatment and give an antiviral therapy for the virus (oral acyclovir). NEVER FORGET to tell the patient to return to you if the lesions erupt or if systemic symptoms are noted [SJS or TEN (which are emergencies) possibility]. Note: the blisters of erythema multiforme are usually noted on the limbs due to type 4 hypersensitivity reaction. Erythema Major SJS-TEN: These are acute and life-threatening situations in which the target lesions grow and turn to bullae forming skin ulcerations thatbegin in the trunk and face and often involve the mouth, the eyes and the genital area (mucous membranes in general). Complications are very serious and can result in multiple organ failure. The patient looks toxic (lethargy,(كسل) evidence,(ازرقاق الجلد) of poor perfusion, cyanosis hypoventilation or hyperventilation, etc.) and a positive nikolsky sign (bullous disease; e.g. SJS) is noted (Nikolsky sign: pushing a bullous to the surrounding healthylooking skin if the bullous affects the healthy skin this means that it is not really healthy and is also involved in the disease and this is a positive result of the nikolsky sign which is characteristic for all bullous diseases). 6 P a g e

7 Ask for history to see if the patient took any drugs that possibly triggered the SJS/TEN (SJS is classically triggered when some certain drugs are given as a bolus dose). The diagnosis is mainly clinical and it can be confirmed via a biopsy. The disease is called SJS when 10% of the skin is involved (3% mortality); if the disease involves 30% or more of the skin it is called TEN (30-50% mortality!). As seen here, in an SJS/TEN patient, the epidermis has been completely detached from the underlying dermis. In the free space between the two layers a fluid gets collected forming the bullous lesion. This is a list of the drugs that have the ability to trigger SJS/TEN (This list is for memorisation): Recurrent Herpes Labialis From now on we will be talking about normal diseases that are quite common. Reactivation of HSV-2 usually causes recurrent herpes labialis (37% of college students at year 1 have this disease and 46% at year 4 in US). 7 P a g e

8 This is usually asymptomatic (or with milder symptoms than primary infection). A common scenario is the patient telling you that they had a tingling/itchy/burning sensation (around 2 days) before the appearance of the vesicles; they d usually resolve within 5 days. In immunosuppressed patients the disease becomes serious (severe mucositis and spread to skin surrounding the mouth) and medications are required. Pathophysiology HSV-1 is more common than HSV-2. Transmission is usually via direct contact or sharing of fomites days after contact the symptoms may appear, but shedding is between day two and day 5 of the contact. Usually the first episode is the worst, the second becomes milder, the third even milder and so on (the immune system begins to know how to deal with it). After the first episode the virus remains dormant in the trigeminal ganglion and it is triggered again with stressors (fever, stress, sun exposure, trauma, immune suppression, hormonal changes (menses), fatigue, etc.) The second image is a more common case than the first. Patients tend to touch the vesicles and scratch them causing them to crust (due to infecting them for example). Treatment: The anti-viral drugs only lower the time of the infection, but do not remove the virus itself (giving acyclovir in the first episode reduces the duration of the symptoms from 10 days to 4 days and the shedding duration to 1 day instead of 5. With recurrence, oral drugs, acyclovir, famciclovir, valacyclovir, etc. reduce the symptoms by just 2 days while topical drugs reduce them by less than a single day!). Is this simple reduction in the symptoms duration worth the risks of giving these antiviral drugs? Not really but we are supposed to follow the guidelines given which (in most cases) do tell us to prescribe a drug Genital Herpes 8 P a g e

9 Very similar to herpes labialis except being on the genital area (so it is sexually transmitted) and the cases are quite large in number (300,000 per year in USA). This disease constitutes around 60-70% of STD ulcers. High prevalence in western countries (12% / 10-30% in sexually active people). Mainly caused by HSV-2 (90%, more severe, more prolonged and more outbreaks) and may be caused by HSV-1 (becoming more common nowadays). Most patients (two-thirds) are asymptomatic, but the virus may still be shedding! Same as labialis, the first episode is the worst (associated with fever, malaise and adenopathy) while the latter episodes become less severe. Once the patient gets infected the virus remains dormant in the sensory ganglion of the affected part. On reactivation, the dormant DNA travels via the axon and erupts. Preceded by tingling/itchiness/burning sensation (like labialis). Lesions are seen around the genital area and the anal area. Primary vesicles remain up to two weeks while reactivations remain for 6-12 days. In the early stages (more common clinically) normal vesicles are seen while in the later stages of the disease they seem to be crusted as vesicles erupt and some bacteria might have entered. Usually the clinical picture is enough for diagnosis, but sometimes HSV PCR is requested. Antivirals only shorten the duration of the symptoms (again follow the guidelines). Low dose anaesthetics and topical antivirals can be given. During pregnancy, the mother might transmit the disease vertically to the child causing neonatal HSV infection which can cause serious complications like encephalitis, disseminated HSV infection or congenital HSV infection which may lead to microcephalus, hydrocephalus or chorioretinitis. You can give the mother a vaccine to avoid this occurrence and if the disease still showed up antivirals could be used. 9 P a g e

10 Active lesions in a pregnant woman may make a caesarean section recommended. Herpetic Whitlow HSV infection present on the finger (either from direct contact or from a previous oral or genital infection) and may be asymptomatic. The patient keeps biting their fingers infecting the area, crusting the vesicles or even causing the formation of ulcers. The patient usually presents with vesicles and regional lymphadenopathy. The main treatment is to prevent the transmission of the virus to other areas [some physicians put a low concentration iodine solution (which has a very strong odour) on the infected finger which prevents the patient from biting that finger!] by, for example, bandaging. Antivirals are to be used in immunocompromised patients and in recurrent occurrences. Tzanck smear could be done. You must be able to differentiate between this disease and paronychia (bacterial). Herpes gladiatorum occurs in wrestlers and rugby players (mucocutaneous infection of surfaces such as chest, ears, face and hands). Paronychia More common in females Usually occurs due to a penetrating trauma (biting of fingers). Bacteria from the skin or the mouth can enter the tissue causing an infection. Infection occurs 2-5 days posttrauma. Local inflammation signs 10 P a g e

11 (redness/hotness/pain/fever) Can progress to abscess formation and nail bed infection which are serious. Pus may be seen (no pus in whitlow). Soak for 15 minutes in warm water or acetic acid soak. Varicella-Zoster Virus Also known as human herpes virus 3. It causes both, chickenpox (initial) and shingles (later stage). Chickenpox 90% of the cases occur in children <13 years old with the peak being between 5 and 9 years old School age. Its peak outbreak is between January and May (cold season). Its incubation period is long: days Can be transmitted via respiratory droplets or via direct contact (or vertical). Some prodromal symptoms appear post the incubation period (Flu-like symptoms) and before the appearance of the rash (which is itchy). As seen in the image, the chickenpox has three phases: it is initially seen as some papules and macules with itching and time the papules are changed to vesicles when the infection has ceased and healing begins the vesicles erupt releasing their content and crusting on the surface and eventually fall off (1-2 weeks from the initial infection). Most of the transmission is by direct contact. Generalised LAP (Lymphadenopathy) is common. You need to tell apart chickenpox from shingles (occurs with reactivation). 11 P a g e

12 The papules appear in crops over 2-4 days. If a patient comes with a small number of red spots and you suspect chickenpox you can ask them to come back after 4 days, if more spots have appeared in different areas then there is a high chance that it is indeed chickenpox (begins on trunk and face and spreads centripetally). Rarely, chickenpox involves the mucosa of the oropharynx and vagina (dangerous). Also rarely, secondary bacterial infections, pneumonitis and encephalitis may occur. In immunocompromised and in pregnancy the disease may be severe. Usually no antivirals are needed (follow guidelines) only reduce the itchiness by giving creams (calamine lotion, oatmeal bath) and antihistamines at bed time. Bacitracin is to be given for bacterial superinfections (impetigo) especially crusted open lesions. (الحزام الناري) Shingles A localised recurrence of varicella zoster (which stayed dormant in the dorsal root ganglia) which causes a unilateral vesicular eruption in the dermatome it stayed dormant in (most commonly T1 or T2 and it also occurs in the face or other regions). In older medicine they called it flame snake and said that if the head of the snake eats its tail the patient dies This is true, if the shingles is bilateral and it progress from posterior to anterior then it could be lethal. Usually shingles is preceded by 2-3 days of pain in the affected area. Both, shingles and chickenpox are contagious. Shingles is very common (1 million cases per year in the US). Mostly peaks at older ages (50-80) when the immunity drops. More common in females (unknown reason). Preceding the rash, numbness along the nerve root, fever and headache are reported. 12 P a g e

13 The rash begins as erythematous maculopapular distinct vesicles erupt. The vesicles turn cloudy after 3-5 days and crust by the 10 th day. This may leave a scar. Resolution may take 2-4 weeks (a very long period). LAP with tenderness is common. PCR is the most sensitive and specific diagnostic test here. Antivirals are used if the patient is immunocompromised (> 50 years old), more than 50 lesions are present or if the shingles is facial or ophthalmic. Pain is to be managed (you can gradually give stronger analgesics, but if the pain is too much you might start with strong ones). Steroids could be used sometimes. Zoster Seine Herpete A rare type of shingles where all the symptoms of shingles are seen except that there is no rash at all making it difficult for the physician and the patient. This variant of shingles is becoming more common. Ramsay Hunt Syndrome That is when the shingles is in the facial nerve. It results in symptoms close to those of stroke leading to misdiagnoses, but some rash in the ear can be noted which tells us that it is shingles. Rapid onset and facial pain are noted and tinnitus and vertigo if cranial nerve 8 is involved. It is seen as a unilateral herpetic rash of ear pinna may cause hear loss. Peripheral facial paralysis occurs. Give antivirals, corticosteroids and pain killers 13 P a g e

14 Herpes Ophthalmicus Occurs when the virus is dormant in the trigeminal nerve ganglion. It reactivates in immunocompromised and old aged people. Hutchinson s sign is typical (two-fold risk of ocular involvement). Can cause eye complications (keratitis, iritis, episcleritis) Loss of vision. You MUST consult the ophthalmologist who will give the patient high doses of antiviral drugs [acyclovir- 800mg 5 times a day for 7-10 days; valacyclovir-1000mg 3 times a day for 1-2 weeks; famciclovir- 500mg 3 times a day for 7 days, (just one of the above drugs )], antistaph antibiotics and corticosteroids may be given (has a risk of corneal perforation, consulting an ophthalmologist is A MUST!). 14 P a g e