Editor's Note: In Part 1 of this series, Those Pesky Rashes: Critical Dermatology Issues in Primary Care, Drs Vega and Lipper discuss the assessment and management of rashes and lesions commonly seen in the primary care setting. In Part 2, they discuss case challenges.
Charles P. Vega, MD: Welcome once again to Critical Issues on Medscape. Today we are covering part 2 of Critical Issues in Dermatology. I am Dr Charles Vega, clinical professor of family medicine at the University of California at Irvine. I am excited to be joined by Dr Graeme Lipper. He is a dermatologist at Advanced DermCare in Danbury, Connecticut. He is also an associate professor of dermatology at the University of Vermont. Graeme, great to see you again.
Graeme M. Lipper, MD: Thanks, Chuck. It's great to be back.
Dr Vega: We are going to be doing something a little different now, something we haven't tried before. Hopefully, it is a little bit more interactive. You have some challenging cases involving rashes or skin lesions for primary care physicians. We have three cases to go through. We will discuss some of the differential diagnoses and how we arrive at clinical decisions for these cases.
Dr Lipper: That sounds like fun. I have some good cases for us.
Dr Vega: I might need your help. I may need to phone a friend.
Case #1: A Child With a Cough, Conjunctivitis, and a New Rash
Dr Lipper: Let's start with a pediatric case that is somewhat topical. I am going to show you a picture of a preschooler who came in for an emergency same-day appointment for a new rash (Figure 1).

Figure 1. Child with new-onset rash. Credit: Wikimedia Commons.
According to the parents, the rash has been present for a day or so, a very new onset. It was preceded by 2-3 days of cough, runny nose, and some bilateral conjunctivitis. There has also been some low-grade fever and a little bit of stomach discomfort. You are presented with this patient with a rash. This is a young child. What do you do?
This is one of those situations where history is quite important. You notice on inspection what we would call a macular exanthem, a rose-colored erythema with macules that blanch on palpation. There is a little bit of periorbital edema. The rash is fairly generalized but is more prominent proximally on the trunk and face than on the distal extremities.
When you ask about the presentation, the mother tells you that the rash started around the child's face and periocularly and then spread to become much more generalized over a 24- to 48-hour period.
You might want to look in this child's mouth. You might find something quite helpful.
Dr Vega: That clue is huge because viral exanthems are always a challenge. This is a good practice point. If you see a challenging rash, sometimes it is helpful to get the opinion of a colleague. With this one, though, you may want to be careful about exposing too many people to this kid, and you should definitely keep him away from other kids.
When you think about generalized rashes, this kid is a little bit old for roseola, but there are certainly lots of enteroviruses that can produce a generalized exanthem. The history is key here. What I focused on was the cough, coryza, and conjunctivitis. Those, to me, indicate that there is a strong possibility of measles. Measles is something that we do see. In California, we had a fairly recent, large outbreak that got national attention. This is a disease, sadly, that is coming back.
I have not actually encountered or diagnosed a case of measles. I am aware of the resurgence of measles, so we are trying to make ourselves more aware of it. But in terms of differentiating this from other types of viral exanthems, are there any other clues? Or does it come down to the history and the specific finding of Koplik spots in the oral cavity? Do you have any other advice for clinicians regarding this case?
Viral Exanthems
Dr Lipper: My pediatric colleagues often make fun of me, tongue-in-cheek, saying that I often tell them, "Oh, yes, it's a viral rash. It will go away on its own." Well, that is often the case with benign, self-limiting viral eruptions. You mentioned roseola exanthem subitum, which is quite common and usually presents with a high fever (Figure 2).

Figure 2. Viral exanthem: roseola. Credit: Science photo library.
But there are some common points to note with all of these rashes. Every patient presents slightly differently. If you are looking at African American or Asian skin types, it is important to emphasize that although erythema is readily visible in patients with light skin, it can be much more difficult to appreciate in children with darker skin tones. You have to factor in the ethnicity and skin type of the patient.
Measles and Rubella
Measles, which was the diagnosis in this case, was brought up because it is topical. I would be lying if I said that I saw a lot of measles cases in Connecticut, but there has been a resurgence, and measles is no longer a problem that we only read about in textbooks. In fact, we talked about morbilliform or so-called measles-appearance rashes primarily when we were referring to a certain type of a drug rash.
When I see this kind of a reaction, my first thought is, "Did this kid get amoxicillin or an oral antibiotic, and is this a type of a reaction?" Therefore, it is very important to look at some characteristic features. The coryza, the barking cough, the conjunctivitis, and the periorbital edema are clues that this is measles. Another characteristic finding of both measles and rubella (German measles) is that the rash typically starts on the face and spreads from the top down in a head-to-toe distribution. You might get a history that the rash started around the eyes and face and spread to involve the torso and extremities. It's almost like a curtain dropping.
Both of these conditions have characteristic enanthems (oral findings), which are important to look at when you are debating whether this could be a condition that would be reportable. It is certainly very relevant in terms of reporting it to your local health department. With measles, you may see Koplik spots (Figure 3).

Figure 3. Koplik spots. Courtesy of Wikimedia Commons.
Koplik spots are tiny, bluish macules on the buccal mucosa that are located anterior to the premolars. These are very apparent and are a very early sign of measles. They often present before the actual exanthem and linger, so they are quite specific. If you see these, you can be pretty confident that measles is your diagnosis.
Roseola
You mentioned roseola, which is probably the thing I see more often, by far. The classic take-home bullet point on roseola is that kids feel much better than they look. They have a high fever and a reddish macular rash that can be all over their body. Often, it gets worse when they cry or have a bath and vasodilate, but the kids are fine. They are playing, smiling, and laughing. They don't look sick. They just have a rash and a history of a high fever. That would be a very good clue that you are dealing with a self-limiting process. In that case, it is caused by human herpesvirus 6. Roseola is something that we certainly see often.
Fifth Disease
Similarly, because we are talking about viral exanthems, slapped cheek syndrome (fifth disease) is another one that I see a lot of. Kids come in with bright red cheeks and a history of fever (Figure 4).

Figure 4. Fifth disease ("slapped cheek syndrome"). Courtesy of Wikimedia Commons.
Slapped cheeks is a pretty characteristic finding, so I doubt that you are going to confuse fifth disease or slapped cheek syndrome with measles. An important take-home message is that it is caused by a parvovirus. If you have fetal exposure, it can be quite dangerous. It's also dangerous if you have certain disorders that make you prone to hemolytic anemia, such as sickle cell disease. There are specific take-home messages for these families. If I saw a child with slapped cheek syndrome, I would make sure that the child isn't around pregnant women while the child is in the acute phase because you wouldn't want to expose the fetus.
Varicella

Figure 5. Varicella. Medscape Drugs and Diseases.
I don't see a whole lot of varicella now that the vaccines are around, but sometimes you will see patients from other countries. I recently had a patient from India who came in with classic varicella—the appearance of a dew drop on a rose petal (Figure 5). You have to keep all of these things in mind, especially when you see international patients who might not get the varicella vaccine like we do in this country.
Pityriasis Rosea
There are other viral rashes that you probably see a lot of. Pityriasis rosea (PR) comes to mind. PR is often mistaken for psoriasis or ringworm because it consists of oval scaly patches that can look a little bit like tinea corporis, like what you would see in a wrestler, except that they are very widespread and all over the torso. The tip-off here is that you will see what is called a herald patch—not always but often. It is a large, scaling, salmon-colored patch on the torso that precedes all of the other smaller patches. Once you see it, you won't forget it (Figure 6).

Figure 6. Pityriasis rosea/"herald patch." Courtesy of the Centers for Disease Control and Prevention.
That is actually the viral exanthem that I see the most. It's usually associated with very little in the way of systemic symptoms, sometimes nothing. Sometimes there is a preceding viral or upper respiratory infection, the type of symptom that, when you ask about it, the teenager says, "Oh yeah, I did have a cough about a week ago," and that is pretty much it. It is a self-limiting process, and we don't really worry about it. Reassurance is generally all that is needed. Topical corticosteroids or phototherapy may be used if someone wants to clear it up and doesn't want red blotches on their skin for a week or two.
Once in a while, I will get a very distraught teenager who says, "I have the prom in 2 weeks. I have a low-cut dress, and I don't want to have all of these red blotches." My answer is to use a light box. It clears up pretty quickly with narrow-band UVB light. Acyclovir was occasionally used in the past, but there is very little evidence to support its use, so I don't routinely treat with it.
Case #2: A Young Girl Develops a New Rash After a Camping Trip
Dr Vega: I am going to say that I'm one for one. Let's go on to the next case. For those of you who are watching, make sure that you play along at home. It is good practice to go through your clinical reasoning with these cases. We have two more to go.
Dr Lipper: This is a young girl who returned from a camping trip to the Blue Ridge Mountains of North Carolina. She reported symptoms of what she thought was food poisoning but came in because they were getting worse instead of better. She had some nausea and vomiting, headache for about 2 days that was becoming quite severe, and she was spiking a fever. Her family noticed the rash in the morning, which was quite alarming (Figure 7).

Figure 7. Rash in a patient with fever. Courtesy of Centers for Disease Control and Prevention.
We have the clinical picture. This is the kind of condition that, as a dermatologist or primary care provider, you want to be able to recognize very quickly because early intervention can be the difference between an excellent outcome and a fatality. This is one of the so-called "dermatologic emergencies." There are some conditions that can be fatal if you don't diagnose them expeditiously. This is one of them. What are your thoughts about it?
Dr Vega: I definitely have a sense of what it is. Thanks again for the assist because the first thing that jumps into my mind, based on the last part of your commentary, is meningococcemia. She is at the right age for infection with meningococcus. The vaccine is certainly not universally applied right now. That can be remarkably helpful. In my mind, that is more of a purpuric rash, but her symptomatology with the headache and fever fit with meningococcemia. I would be very concerned about that possibility because that is a case that can go south very quickly.
Dr Lipper: I am very glad that you brought it up because that is a prime differential on this one. I would point out the camping history and the fact that she was in the Blue Ridge Mountains. The two things you want to think of when you are confronted with a petechial skin eruption in a sick individual are meningococcemia, as you said, and one other entity, which is a rickettsial illness.
Dr Vega: Rickettsial diseases are another challenge because they are certainly not something we see every day. I heard the camping history loud and clear. I figured that there was a reason for that detail to be included in this case. What is going on here is either Lyme disease, ehrlichiosis, or Rocky Mountain spotted fever (RMSF). Looking at the picture and the clinical scenario, I would say RMSF. It makes the most sense because it doesn't seem like a Lyme rash to me.
Rickettsial Diseases
Dr Lipper: Let's review rickettsial illnesses because it is obviously important to be familiar with these illnesses. For RMSF, the classic triad is fever, history of a tick bite, and a characteristic rash. It is important to note—and this is true of all arthropod-borne conditions—that you don't always get a history of a tick bite. With RMSF, only about 60% of patients can recall a tick bite. A large percentage of people don't give you that history, and you may not see a visible punctum. Some of the vectors, depending on the region of the country, can be ticks that attach to the scalp. With Lyme disease, where you are mostly dealing with Ixodes scapularis, you usually see a pretty prominent truncal rash but not always.
In this case, the tip-off would be the acral location of petechial lesions in an individual who has been in an endemic area. Typically, the Blue Ridge Mountains would be prime territory for this, but there is a pretty widespread distribution of ticks that carry the Rickettsia rickettsia organism. They can be found in North Carolina, Virginia, Maryland, as well as places like Michigan and Alaska. Ironically, in the Rocky Mountains in Colorado, they are not as common as in the Appalachian region and in the Blue Ridge Mountains. That is where most of these cases occur, but they also occur in places like Montana, Georgia, and Michigan. The outdoor exposure history—the hiking history—is helpful.
Another trick to making this diagnosis would be to look at the systemic symptoms. Remember when I said to look at your patient and see how ill they are? This would typically be someone with a lot of systemic symptoms—someone who is lethargic. This organism infects endothelial cells, causing a systemic vasculitis. You don't get petechial lesions just in your skin; they are a reflection of what is happening throughout the body, including in the central nervous system and kidneys. Therefore, it is an emergency that, if it progresses, can lead to acute renal failure, encephalopathy, disseminated intravascular coagulopathy, sepsis, and death.
One hopeful fact about RMSF is that if you detect it early and start appropriate antimicrobial therapy—which in this case is doxycycline 100 mg twice/day, or you can split the dosing or give it intravenously as tetracycline—you can get rapid resolution and a much better prognosis. You can lower morbidity and mortality rates to under 3% if you treat promptly and appropriately.
This is also the type of patient that you would want to hospitalize. By the time they are getting petechial lesions on their skin, they are also at risk for systemic involvement, and they might need a lot of supportive care—basically, intravenous medications and monitoring of their kidney function. This would be someone that you don't want to send home with reassurance. You want to admit them and put them on an appropriate antibiotic.
Meningococcal Disease
Dr Vega: And they might need further urgent evaluation for meningococcus. We know that RMSF can be quite dangerous. Meningococcus is another true emergency, and it needs to be evaluated at a higher level than can be provided by your basic medical office.
Dr Lipper: Absolutely. You are going to make the news with a case of meningococcemia. That is a highly contagious respiratory illness. RMSF is an acute condition for the person who has it, but meningococcemia is an epidemiologic emergency. Anyone who is exposed can get this.
Meningococcemia is caused by Neisseria, a gram-negative bacteria that is airborne and acquired through exposure to respiratory droplets. It is important that you brought up that differential because you certainly also get ecchymotic or dusky, purplish lesions with meningococcemia. In this case, it is because of intravascular thrombosis, disseminated intravascular coagulation. When you see someone with meningococcemia who has skin lesions that are dusky, it is already pretty serious (Figure 8).

Figure 8. Meningococcal lesions. Credit: Alamy.
If this girl had presented with meningococcemia, we would worry about people in community environments such as colleges or infirmaries, where respiratory illnesses are easier to spread. I would also worry about meningococcemia if she had other signs consistent with this infection such as headache as well as neck stiffness and photophobia.
You wouldn't be faulted for covering for both of these diseases when beginning treatment, and that is often what happens. While the workup is ongoing, these are both conditions that are covered with appropriate antibiotics. Therefore, you give supportive care and antibiotic coverage. This is something that you diagnose based on the clinical signs and epidemiology. You wait for serologic confirmation after the fact. It's nice to say, "Oh, I guess that wasn't RMSF, but I treated for it anyway," or "I guess I overreacted to that one. That was viral meningitis instead of bacterial meningitis, but at least we covered that possibility."
Dr Vega: Yes, absolutely. We don't want to get behind on these infections.
Dr Lipper: You don't want to wait for the blood work or the biopsy results, even if they are rushed. By the time you get those back, these patients should already be on appropriate therapy.
Dr Vega: Thank you for that insight. I am going to count myself as having 1.5 out of 2 accurate. Let's go to case number three. Let's finish strong.
Case #3: A Pigmented Lesion
Dr Lipper: One of the most important consultations for us is a pigmented lesion. As dermatologists, we see a lot of referrals for pigmented lesions on the skin. Obviously, when we get those referrals, the concern is that we are dealing with a malignant melanoma, the most serious type of skin cancer and, fortunately, the rarest. But incidence is growing every year, and we are seeing a pretty high incidence, especially in people we used to not expect to see it in. Younger women who do indoor tanning are getting melanomas in their 20s now, and it is always shocking when I see this, but we see it a lot.
When you are dealing with a pigmented lesion, that is always going to be your first thought (Figure 9).

Figure 9. Pigmented lesion-melanocyte. Credit: Science photo library.
Is it a melanocytic lesion, meaning a lesion that contains an increased number of melanocytes?
Or is it a mimic, something that is benign but can look quite concerning, like a seborrheic keratosis, which is a barnacle-like thickened lesion that usually comes in clusters with more of a stuck-on appearance (Figure 10)?

Figure 10. Pigmented lesion-seborrheic keratosis. Credit: Science photo library.
We get a lot of referrals for pigmented lesions. We magnify them with a dermatoscope, which uses either polarized light or a modified water or oil immersion lens to magnify the external features of a pigmented lesion. It is a very helpful device for distinguishing between a melanocytic lesion and normal skin with a nonmelanocytic lesion. That really helps dermatologists to go down the therapeutic ladder. Do we biopsy this? Do we rush the biopsy? Do we do an excisional biopsy? Do we do a shave biopsy? These decisions are often guided by what we see.
We can save a lot of angst for our patient with a simple bedside technique. For instance, a vascular lesion like a cherry hemangioma can look very dark and purple, especially in certain locations. If someone was running and has a blood blister under their nail ("talon noir") or on their heel, you can look under your dermatoscope and confirm that it is blood. You can see vascular lagoons or little petechial hemorrhages and say to them, "Don't worry. If it doesn't go away, call me, but it is a bruise or a benign hemangioma. If you want, I can treat it cosmetically, but it causes no harm to you."
For primary care providers, especially if you don't have easy access to a dermatologist, investing in a dermatoscope is very helpful. Honestly, I think you would probably get more out of that than you would out of an ophthalmoscope. It is a good investment. It helps to triage lesions to determine which ones require further evaluation—which usually means a tissue biopsy—and which ones can be monitored and patients reassured.
Melanoma

Figure 11. Melanoma. Credit: Eric Ehrsam, MD, dermoscopy.
Dr Lipper: Now, I believe this lesion is a melanoma (Figure 11), if I am not mistaken, and quite an ugly one. It is a raised, somewhat exophytic lesion. This is the type of lesion that needs an urgent referral for biopsy and definitive treatment, which would usually be a wide, local excision and often lymph node evaluation, depending on the depth of invasion of the melanoma.
One of the questions that a lot of primary care providers might have is: When do we biopsy these, and when do we refer them out? Is that something that would be on your mind when you see one of these?
Dr Vega: For this lesion in particular, it could have been classified as benign. The point is well taken on the dermatoscope and on being cautious. But at the same time, we can't biopsy every melanocytic lesion that we see. That is my question. Using caution as a guide, we refer for biopsy, but even then, there are different layers. How do you biopsy? Is it okay to do something less invasive? I am sure that with a lesion like the one you are seeing, you are not going to necessarily lead off with doing the wide resection with lymph node assessment, but that is something you will move towards as you make the diagnosis.
One of the challenges I face is the promptness of the referral because referrals can linger for weeks or even months if the patient cancels, for example. I am not necessarily informed about that cancellation. Shared decision-making and a little education go a long way. From your end of things, you don't necessarily want to overbook six patients in your clinic who were referred urgently for probably something that is quite benign. How does that sit in terms of your actual clinical practice pattern, and what is the best way to move forward—maintaining vigilance but also creating efficiency in a patient-centered approach?
Dr Lipper: That is a very good question. I think it helps, in this case, to have a good relationship and rapport with a dermatologist. For instance, this isn't a referral that you would want to bury and have seen in a month or two if it is something that is alarming to you. In our practice, at least, we have our nurses triage and directly tell us if there is a lesion that is of significant concern to a primary care provider or a patient, and we will bring a patient in in an expedited fashion for that. I think that is very important. If you have access to a dermatologist in your community, make sure that you have a good relationship. Some things need to take priority, just like with any triage situation. We have very excellent primary care providers in our area who know how to distinguish between a typical benign seborrheic keratosis and a suspicious pigmented lesion. If we get a call, you better believe that we are going to make it our business to get that person in. That would be ideal. It would be a same-week appointment for a lesion of concern to you.
Diagnostic Devices
If that is not feasible and you are in an area where you don't have those resources, it would be very helpful to have a dermatoscope. It's a simple investment that is very helpful, even with an online course (Figure 12).

Figure 12a. Pigmented lesion with the naked eye. b. Under dermatoscope, lesion has characteristics of a benign nonmelanocytic lesion (seborrheic keratosis). Credit: Eric Ehrsam, MD, dermoscopy.
There are courses all over the place nowadays on how to use a dermatoscope to distinguish between benign nonmelanocytic lesions and a melanocytic lesion. You look for very characteristic features. It is pattern recognition—not difficult pattern recognition—to decide whether something is worrisome or not. (Figure 13).

Figure 13a. Pigmented lesion with the naked eye. b. Under dermatoscope, lesion has characteristics of melanoma. Credit: Eric Ehrsam, MD, dermoscopy.
It is difficult to decide whether it is a dysplastic nevus, melanoma in situ, or something that is worrisome for regression, but if you are looking to determine whether it needs to be removed or not, the distinction can be made with a relatively low investment in a dermatoscope and a little bit of training.
Today, there are many assisting devices that use visual algorithms to give you a probability of a lesion being malignant. MelaFind® and other devices use absorption spectrophotometry to look at a lesion. These are really cool devices that use image analysis and an algorithm to provide the probability of a lesion being a melanoma. You point and click, and it tells you the likelihood. They have been studied and compared in terms of sensitivity and specificity with board-certified dermatologists. As much as I would like to say that we are better because we are human, and we spent all this time training, the data don't say that. The data say that the sensitivity and specificity are better with these devices. Whether they should be adopted for widespread use is very controversial because these are expensive. It would be a massive burden on healthcare settings. I think it is more important to have high sensitivity rather than specificity. I am worried about missing a melanoma, so if a device gives me a little more specificity but I am going to biopsy something anyway, it doesn't help me as much.
Dr Vega: It hasn't changed patient management.
To Biopsy or Refer
Dr Lipper: It hasn't changed management. The other thing I would like to address is the issue of performing a biopsy as a primary care provider vs referring. The important take-home message here is that, with melanomas, the thickness of the lesion is very important for prognosis, determining appropriate management, how wide of a margin should be removed, and whether sentinel lymph nodes should be evaluated. So when in doubt, I would say that if you have the ability, excisional biopsy is always preferable.
However, excisional biopsy isn't necessarily going to have to be with a scalpel and sutures. You can take a very deep saucerization-type biopsy. As long as you are biopsying down into the deeper or reticular dermis, I think you are getting the prognostic information you need. I know there is a debate among dermatologists about whether you need to do a full-thickness excisional biopsy on every suspicious pigmented lesion. But certainly, within standard of care, taking a deep saucerization-type biopsy would give you the entire lesion.
The pathologists that I have talked to would rather get the entire lesion than a small punch biopsy of part of the lesion, which might not be representative at all. You could punch through a melanoma and get a melanoma in situ as the result from what was actually a 1.5-mm invasive melanoma. You could be punching the edge and taking a tiny sample.
If you are going to do biopsies, be comfortable with taking a relatively deep biopsy. You really need to be down to about 2 mm in depth to make sure that you get the prognostic information you need.
Dr Vega: Great. I think that is certainly what we pursue in our practice when we are looking at pigmented lesions. But for sensitive areas, biopsies that appear trickier, or for truly suspicious lesions, those are urgent referrals to dermatology, every single one of them. Generally, we have had a very good response, and folks are very dedicated—both on the primary care side and the dermatology side—to getting the patient the best care they can expeditiously.
That is our time for this segment. Totaling it all up, I think I did okay, but you did great. Thank you very much for your assessment. Hopefully, those in our audience saw from these cases some conditions that really do affect your practice, although maybe not on a regular basis. Measles is not something that you are going to see very often, but it is certainly something about which we have to be aware. We talked about rickettsial diseases, differentiating them from meningococcemia, and how these are both emergent conditions. The last one is something that we all see. "Hey, what is up with this mole?" It is always the question that the patient asks right before they are leaving the clinic, or they actually come back from the parking lot and say, "I forgot to mention this, doc."
So take the time to do the right kind of exam. As you mentioned, Graeme, the more detailed exam could really be a lifesaver for patients. Thank you again for all of your great advice. We will look forward to seeing you next time on Critical Issues on Medscape.
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Cite this: Charles P. Vega, Graeme M. Lipper. Those Pesky Rashes and Lesions: Part 2 - Medscape - Nov 23, 2015.
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