Episode 42: Fever with Rash- Dermatologic Clues and Diagnosis

Welcome to Head Pods, the audio podcast from the Department of Intel Medicine at AFMC. In our last episode, we spoke to Karnal Anil Patnagar, head of the department of dermatology at AFMC about Dermatological Disorder, an emergency of acute skin failure. Continuing with that series, today we shall be discussing another very relevant topic of fever with rash. Fever with rash happens to be one of the most common theoretical syndromes in general practice, which is encountered by both pediatricians, general medicine specialists as well as medical doctors. And I'm sure this topic will be of great benefit to our students. So, welcome back Anuj. Thank you, sir. So, what are the most common infections where you encounter patients coming to you with fever and rash when it comes to children as well as adults? In children, the most common cause of fear with rash are viral exemptions such as measles, rostrum, varicella, erythema infections, few causes, bacterial causes like stefinococcal scarlet skin syndrome, scarlet fever and Kawasaki. While in adults, viral infections like dengue, chicken munia, herpes, osteoarthritis are prevalent in our country. The other causes are drug reactions, autoimmune disease like lupus, bacterial infections like meningococcemia, toxic shock syndrome, syphilis, Lyme's disease and reticent infections. The presentation can differ with age, severity and comorbid conditions. Right. So, the reason why in certain infections or certain conditions with fever, rash accompanies may be due to the infection, inflammation or immunological mechanisms. So, when it comes to systemic inflammatory responses which contribute to this rash with fever, how do we do that? What is the mechanism? In febrile illnesses, systemic inflammatory response involves the release of cytokines and various mediators which cause vasodilatation and increased vascular permeability like in dengue. The immune response to virus can cause characteristic macropepera rash due to immune complex deposition and capillary leak syndrome. In chicken munia, the rashes can be due to the direct viral effect and various immune responses. These mechanisms highlight the complexity of the inflammatory response in different infections. Right. And when it comes to pediatric practice, viral exanthymatics, fevers are one of the common illnesses in children. So, what are the immunological mechanisms which underlie these rashes? So, the viral exanthymes involve systemic immune response to particularly viral antigen that leads to the specific cutaneous manifestation. Whereas, in drug rash, it results from hypersensitivity reactions wherein the immune system targets the normal cell due to drug related antigens. This can involve various types of gel and tube hypersensitivity reactions from one to four, leading to diverse manifestations from mind to severe, including Stevens-Johnson toxic blood and neck illnesses which are critical to differentiate from other viral exanthymes. Now, in the current time of the year, we see a lot of patients with dengue fever and often you find these patients have macular, papilla rash or some of them have PTK or even papura. So, what is the pack of physiology and what is the difference in the mechanism as far as these two different types of rashes are concerned? So, the particular rash like in daily can be due to capillary fragility and thrombocytopenia resulting in small pain point hemorrhages under the skin. This differs from macular paparage which is more inflammatory and involves immune cell infiltration into the skin such as other viral exanthymes. Recognizing these differences helps in diagnosing the underlying infection and assessing its severity. Right, and in certain infections that we see especially the exanthymitis fever and even viral infections, you find that this rash initially starts off in one pattern and then evolves during the course of the disease. So, what are these typical patterns that you see in these infections? Like in measles, the rash typically starts on the face and then spreads downwards often accompanied by coplic spots in the mouth. While in rubella, it presents with a similar but it is of milder variant and it is associated with lymphedemopathy. In kidney, the rash may start as macular paparage or particular rash often with an initial white eye lens in a sea of red appearance. The rash occurs in the fibride face that is the second and seventh day of illness. It is prurotic, dense, diffuse macular per rash. 30% of the patients will have mucosal involvement including apthasulsors and posterior or pharyngeal erythema. The patients who progress to the critical phase in kidney are more likely to have pettichy, which reflects endothelialis function and coagulation disturbances. In chicken vinaigrette, the rash is commonly found in the younger age group which is fine macular paparage exemptant which appears 48 hours after the fever onset. The rash becomes generalized, involved palm and soul. It is prurotic and there is a delayed development of hyperpigmented malarash in these two weeks after the infection which is known as checksign. The other variants include the rickettsia fever in which the rash initially starts on wrist and ankle, involved palm and soul and then spreads centripetally to arms, legs, trunk and face. The initial rash in rickettsia fever is macular paparage which goes on to become particularly as the disease progress. In bacterial endocarditis, there can be pettiti, splinter hemorrhage, January legion and osloves note. Whereas in many cookable infections, the early legions are macular but there is rapid increase in the number of pettichial or percoral legion on distal extremities and trunk which spare palms and souls. In toxic shock syndrome, the rash is diffused erinatus. Later on, there is a descombination which involves palms and souls. Right. So, with this background, it is the general understanding our students would have about why rash happens in certain infections and what are the patterns that they should be aware of considering various types of infection. So, with this background, if you move on to a patient. So, when you are approaching a patient who has fever with rash, what are the key clinical features that one needs to consider? The key features include the rash onset relative to the fever, its distribution, morphology, progression and associated symptoms like lipid and apathy, nipus and involvement and systemic toxicity. In the topical regions like India, we consider additional factors like exposure to mosquitoes, recent travels within or outside the intimate areas and history of outbreaks. Always assess for the signs of complications like hemorrhage or joint pain which are critical in these settings. One important question that we have always been asked as students and probably gives a lot of information is the timing of rash appearance in relation to fever which gives us an idea about underlying disease. So, can you explain it to our students about how you sort of narrow down your diagnosis based on timing of rash in relation to onset of fever? The timing of rash appearance can help diagnose various infections like in measles. The characteristic rash appears three to four days after the fever onset while in daily the rash typically appears two to seven days after the fever onset. In chicken vinyan, the rash appears with fever or after a few days. While in rickettsia fever, we generally have two to five days after the fever. So, in this there is timing of rash which is very, very relevant for initial diagnosis. Right, and one very important aspect of history taking especially in relation to infections is the history of recent travel or vaccination. So, when it comes to fever accompanied with rash, how are these historical factors important? Recent travel in endemic areas, exposure to vectors like mosquitoes and contact with individual with known infections are crucial. Vaccination history for many diseases like measles, rubella, Japanese encephalitis, many gukkukai is very important. Knowing these factors helps in identifying the cause of fever with rash and implementing appropriate preventing measures. Right, so moving on to examination from history, when you are looking at a patient with rash, how does it help you to look at the distribution of the rash and the morphology? And how does it then narrow down your differentials? Rash distribution and morphology provide a very vital clue. For example, a macropepera rash with petiki suggests a dinghy. Resicuera rash suggests varicilla. Chicken vinyan rash is often macropepera and widespread. Presence of nodules on shin denotes erdemar nodosum. We can find target regions and various regions which can suggest erdemar deformy. So, these schemes help the tailor, we can tailor the diagnostic approach and management strategy in our settings. Right, now as the initial contact with patients, one thing that is very important is to pick up the red flag signs so that we do not miss a severe disease underlying a patient who has come with fever and rash. Now, what are these red flag signs that our young officers be aware of while approaching a patient with fever and rash? The red sign includes severe abdominal pain, persistent vomiting, mucosal bleed, lethargy, altered mental status, hypertension and rapidly spreading rash. These signs warrant immediate medical evaluation and aggressive management. As they suggest, severe condition like dinghy hemorrhagic fever, dinghy shock syndrome or toxic shock syndrome which are very prevalent in our areas. Right, so now moving on to diagnosis followed by the clinical evaluation that is involved in time. What are the initial lab investigations that you would consider in a patient with fever and rash? Initial tests include a complete blood count to assess for leukopenia, thombocytopenia or eosinophilia. Lever function tests, liver function tests and serum electrolytes can assess the extent of systemic involvement. Serologies, fortility, chicken pinia and other endemic viruses, PCR for viral detection and blood culture for bacterial infection are essential. These tests guide further management based on suspected infection. Right, so one of the important modalities of an investigation in dermatology practice is skin biopsy and this is an invasive procedure. So in which situations would you recommend that skin biopsy be done and how does it help you? Genital skin biopsy is indicated when the diagnosis is unclear, the rash when it is atypical, it is severe or when conditions like vasculitis or drug reactions are suspected. Skin biopsy is really special to path changes such as leukocytoglastic vasculitis, immune complex deposition or trigonocyte necrosis which provide valuable information for diagnosing infections or drug rash and guide further management. Right, so and what about the role of serological tests, whether it is to do with infections or with immunological diseases, how does serology help? Serological testing for specific IgM and IgG antibodies against pathogens like dengue, chicken pinia, Zika virus should be interpreted based on timing of illness. IgM typically indicates a recent infection while IgG suggests fast exposure or immunity. Serology should be performed when clinical feature and epidemiology suggest a specific infection which help to confirm the diagnosis and management. Right, so unlike other specialties where imaging plays an important role, when it comes to these kind of disorders, is there any role for imaging? Yes sir, imaging has a definite role in directly evaluating fever and rash but can be useful for assessing complications and associated condition. For example, a chest x-ray may evaluate pneumonia in varicella or in measles while ultrasound may detect fluid accumulation in dengue shock syndrome. So, imaging helps to identify the complications and guide management. And also very importantly, what is the role of molecular diagnostic methods now which are so common especially something like PCR? PCR is valuable in rapidly detecting various viral and bacterial pathogens like dengue, chicken pinia, Zika, sermonelotiphy or other liquid sealed species. It is a highly sensitive and specific providing quick results that are very critical in managing febrile illnesses especially during outbreaks. So, from all this that we discussed till now what I can conclude is that fever with rash is a fairly clinically diagnosable condition. We should have some differentials in our mind considering the historical aspects as well as examination findings. And of course these investigations can help us further narrow down these diagnosis. So, coming down to the management aspects of it, empirically how do you approach a patient with fever and rash? Empiric therapy should be regarded by the clinical presentation, suspected pathogen and its regional epidemiology. In patients with fever, rash and hemorrhagic symptoms, empiric therapy may include fluids, antibiotics and close monitoring for dengue. If a battery infection is suspected, broad spectrum antibiotic may be indicated. While, empiric antiviral therapy such as acyclovir for suspected healthy posture can be considered in certain cases. A cautious approach with supportive care and close observation is crucial until a definitive diagnosis is made. And what is the role of drug therapy like antivirals or antibacterials? Antiviral therapy is indicated for specific viral infections where effective treatment are available such as acyclovir for healthy simplex virus, varicella justovirus for dengue, no specific antiviral exist. So, management focuses on supportive care including fluid management, monitoring for complications. Antibacterial therapy is critical for bacterial causes of fever with rash such as bifert fever, menopocal fever, detexil fever etc. These therapies should be initiated promptly when the battery infection is suspected to reduce morbidity and mortality, particularly in life-threatening conditions. Empiric antibiotics might be considered in our settings if there is high index of suspicion for battery infection while awaiting diagnostic confirmation. One problem with drugs is that they themselves cause rash in many situations and we often see patients with fever and rash who have taken some drug after the onset of fever, most likely say an antipyretic, anti-inflammatory or some antibiotic which causes this rash. So, that also I think should be kept in mind but what we are more concerned about is what we discussed even last time in acute skin failure is conditions like Steven Johnson syndrome or Dress syndrome. These are more severe and can be fatal. So, in a patient who comes with fever and rash, how do you manage these patients especially when you are suspecting these severe situations? If we have a pain or very good history in which there is a relation between the taking of drugs and the appearance of rash, the management involves immediate discontinuation of suspected offending drug. Supported care in a hospital setting often end per unit or in ICs necessary for SJS-10. This includes fluid and electrolyte balance wound care, pain control and prevention of secondary infections. For Dress, that is drug reaction and muconphilia and systemic symptoms, corticosteroid may be considered especially if there is organ involvement. Early recognition and withdrawal of offending drug are very crucial to reduce morbidity and mortality. Awareness of common drugs causing hypersensitive reactions is very essential. And other than the definitive management, often the patients are more concerned about the rash and there is some kind of supportive care that can be given along with the definitive treatment. So, in such situations, especially in severe or complicated cases, what are the supportive care recommended? Supported care measures include adequate hydration, antibiotics, analgesics and nutritional support. Skin care to prevent secondary infection particularly if the rash involves open lesions is crucial. In severe cases such as daily plasma leak, aggressive fluid management is essential. Monitoring for signs of shock, bleeding, multi-organized function is essential. In conditions like SJS-10, wound care, protective isolation to prevent secondary infection are vital. Supported care must be tailored to the specific need of the patient and the nature of fever and rash. A large subset of patients in the hospital are immunocompromised, be it due to infections like HIV or if they are on say immunosuppression for post-transplant setting or lot of treatments nowadays require immunosuppressive drugs. So, in such patients when they come with fever and rash, how do you approach? In immunocompromised subsets, the differential diagnosis is broad and include various opportunistic infections such as cytomegalovirus, fungal infections like histoplasmosis, various atypical mycobacterial infections. Empiric therapy may need to be more aggressive and should cover a wide range of specifications including antifungal and antiviral. Early involvement of infectious disease specialists and more aggressive diagnostic testing like biopsy, PCR, culture from various sites are warranted. Preventive measures such as prophylactic antimicrobial and strict infection control practices are also more critical in these patients due to their increased risk of severe and unusual pattern. And coming to the complications like patients who have fever with rash, what are the potential complications that can happen and how can you sort of anticipate or prevent them? Complications depend on the underlying cause but can include secondary victim infections, dehydration, multi-organ failure, sepsis, long-term sequelae like scarring, pyromanic changes. Complications like dengue hemorrhage fever, shock syndrome require early recognition and intervention. Preventive measures include early diagnosis and treatment of the underlying cause, vigilant monitoring and supporting care is required. Right, so two major subsets that come with fever and rash are one, of course, the viral exanthematous fever and the other is bacterial infection which also can manifest with rash. Now, between the two, how do you differentiate as far as the prognosis is concerned? Viral exanthems generally have a good prognosis with supportive care, though certain viruses like dengue measles can lead to severe complications particularly when in immunocompromised individuals or those with coexisting conditions. Vectric infections like menobococinia, typhoid, scrub typhus have a more guarded prognosis due to potential for rapid progression to sepsis and multi-organ failure. Early recognition and treatment are key to improve outcome. Viral like dengue, typhoid can sometimes have a very high mortality rate if not prompting and appropriately treated. So, one of the complications that you mentioned about patients with fever and rash was superimposed bacterial infections. So, in which settings should one anticipate this and what are the factors which influence development of secondary bacterial infection? The factors include the patient age, his immune status, presence of comorbidities like diabetes, malnutrition or severity of primary illness, impurity of skin barrier and exposure to invasive medical procedures or devices. Environmental factors like high humidity, poor sanitation can increase the risk of secondary bacterial infections, dose monitoring, good hygiene, good skin care and prompt treatment of secondary infection or complication can help mitigate these risks. So, coming towards the end of this talk, now this thing is very common and fever with rash and patients would come, especially younger children and the parents are obviously burdened. So, as far as educating them or counseling them about this condition and its long term outcomes, what you need to tell them? Counseling should be tailored to the specific diagnosis and diagnosis. For various self-limiting viral exemptions, reassurance about the typical benign courses appropriate. But for more severe conditions such as deni or SGS10, we have to discuss the potential long term complications. So, it is essential to provide information on signs and symptoms that warrant follow and emphasize preventive measures like vaccination and avoiding known drug triggers. So, educating about vector control, hygiene practice can prevent further infections. So, one of the most important purpose of this educational activity that we do is to educate our young doctors in developing a high index of suspicion for these kind of conditions so that they can pick it up early and manage. And one important aspect of our decision making in this problem is about which patients to hospitalize and which patients to treat as outpatient. So, in a patient with fever and rash, how do you take that decision? Indicators for hospitalization include hemodynamic instability, altered mental status, severe dehydration, very high fever, extensive or rapidly spreading rash, signs of systemic infections like sepsis and DIC and suspicion of severe or life threatening condition like daily hemorrhagic fever, menoproxenia or SGS10. Age extremes that is infants and geriatric population, various immunocompromised status and comorbidities increase the risk of complication and may lower the threshold for admissions. Infections like daily and chicken guinea are highly prevalent in our country so early hospitalization may be indicated to manage complication effectively. So, like we always teach our students that you must have a high index of suspicion and whenever in doubt, you must admit and follow up the patient because there are certain conditions which can rapidly deteriorate like you discussed about SGS10. So, very comprehensively covered topic of a very common nature in clinical practice. What are the key takeaways that you want our listeners to take home? So, the Medical Office must develop a framework for discerning life threatening from denying exanthems which comprise the majority of our OPDs. Comprehensive history and physical examination are essential for diagnosis of fever with rash cases so as not to delay antimicrobial and supportive care. Recreational infection is the most common illness in our country. So, doxycycline remains the choice of antimicrobial in both adults and pediatrics but it is frequently misdiagnosed condition. Dengue chicken guinea are now the most important endemic RORS infections so the focus on assessment of Dengue is essential to decrease the mortality. Early antimicrobial coverage is necessary for treatment and for reducing mortality for rapidly progressive staphilococcal scarlet skin syndrome, toxic shock syndrome. Meningocopsinia poses high risk to targeted population in areas of concentrated human congregation. Reduced infection rates are successful through various vaccination campaigns and early chemo-profile access. The differential analysis of fever with rash should also include life threatening, non-infectious condition and various other endemic infections, infectious disease. What is important to remember is that one should be aware of what are the infections prevalent in the community and in the pace of work where these doctors function because that will give you immediate clue and you can narrow down your diagnosis. And of course to have a very keen eye for a patient who is not looking alright and is likely to deteriorate and have of course a high index of suspicion for severe skin diseases which can lead to conditions like acute skin failure. So I think we've covered this topic well Anuj and I'm sure this discussion will have a lot of importance for learning amongst our students. As usual we request them to come back to us with any questions or clarifications that they may require and of course we will always seek your time for discussing such similar topics in future as well. So thank you very much. Thank you Brigadier Mipu sir for wonderful academic discussion on a very relevant topic.