Red Disorders: Red Papules and Nodules
Peter J. Lynch
Anogenital disorders that present as red papules or nodules are most often either neoplasms or inflammatory lesions. Vascular neoplasms tend to present as bright red, dusky red, or violaceous papules and nodules with sharply demarcated borders. Red, nonvascular neoplasms are also sharply marginated but tend to be lighter red in color. Inflammatory papules and nodules are most often medium to dark red toward the center and tend to fade to light red or pink peripherally. They usually are less sharply marginated than red neoplasms. Most of the lesions considered in this chapter lack scale and therefore are smooth surfaced both visually and palpably. Many skin-colored papules and nodules may appear pink or red at times because of secondary inflammation or increased vascularity. This is particularly notable in patients who have a light complexion. Therefore, when encountering pink or red papules or nodules, the clinician may also need to consider the skin-colored disorders from Section A, Chapter 7. Note that some red disorders may present with a mixture of papules and nodules. In such instances, try to determine whether either papules (Section A) or nodules (Section B) represent the dominant lesions. However, at times, a mix of papules and nodules is present, and for this reason, disorders in both sections may have to be considered.
SECTION A: RED PAPULES
Folliculitis
Bacterial, candidal, and dermatophyte folliculitis can present as small red papules (Figs. 6-1 and 6-2). The lesions are generally multiple and are often clustered. Many times a few of these lesions will have a white or yellow-white pustule at the summit. This distinguishing feature, followed by appropriate KOH preparation and/or culture from the pustule, allows for establishment of the correct diagnosis. The primary discussion of folliculitis can be found in Chapter 10.
Keratosis Pilaris
Clinical Presentation
Keratosis pilaris (KP) is a noninfectious form of folliculitis. It has been extensively reviewed recently, and much of the information that follows is based on that review.1 KP is a very common condition often occurring in an autosomal dominant pattern. There is a slight male predominance. It is more common in children and adolescents where the prevalence may be as high as 30%. KP spontaneously resolves through the teen years, and with one exception, it is not often encountered after the fourth or fifth decade. The exception revolves around what we believe is its common presence on the buttocks in adult women where it is all too often misdiagnosed as bacterial folliculitis.
The clinical appearance of KP is that of minute (1-2 mm) closely set, clustered papules. Some, but not all, of the papules will have a small hair emerging from the summit of the papule, and it not uncommon to find a few white-summited papules intermingled with the more typical completely red papules (see the following paragraph). All of the lesions are approximately the same size, and they are spaced equidistant from one another (Figs. 6-3 and 6-4). This lends a monomorphic appearance to the process and is a helpful diagnostic clue.
In those individuals with the least severe involvement, the papules may be skin-colored or pink, but in most patients, both the papules and a narrow halo around them are distinctly red. A few of the larger lesions may be capped by a firm, solid, white summit (pseudopustule) consisting of compacted keratin retained in the follicular orifice. If this solid white “ball” of keratin is scraped away, it sometimes contains a fine, rolled-up hair within it. The most commonly involved sites for KP are the upper, outer arms and thighs. The buttocks are also frequently involved, and in this location, it is often misdiagnosed as bacterial folliculitis. There is a sandpaperlike, slightly rough, feel when the fingertips are lightly passed over clustered lesions. KP is usually asymptomatic though, especially in atopic individuals, pruritus can be present.
Diagnosis
Keratosis pilaris is diagnosed on a clinical basis. The key features include (1) a large number of closely set homogeneous papules, (2) location on lateral, upper arms, thighs, and buttocks, (3) long duration with little or no change in clinical appearance, and (4) failure to respond to antibiotic therapy.
 Fig. 6-1. These red papules represent a Staphylococcal aureus infection of the hair follicles, although the buttocks are a common location for irritant folliculitis as well. Although folliculitis is considered a pustular condition, most lesions are papules, since the pustule is often subtle and ruptures early. |
KERATOSIS PILARIS Diagnosis
Clustered, small (1- to 2-mm) red papules
White-capped, solid keratotic summit on a few scattered papules
Hairs emerging from the summit of some papules
Equidistant spacing of all the papules
Location on the lateral arms and thighs and/or on the buttocks
Rough, sandpaperlike feel on palpation
Failure to respond to antibiotics
 Fig. 6-2. Shaving is a common cause of irritant folliculitis, with erythema at the base of each shaved hair. |
 Fig. 6-3. Keratosis pilaris exhibits monomorphous, follicular papules with a keratotic plug that gives the skin a sandpapery texture; although sometimes skin-colored, many patients exhibit erythema as seen on the buttocks of this patient. This patient also had typical keratosis pilaris on the lateral, upper arms. |
Pathophysiology
Keratosis pilaris is caused by excess keratinization (keratin plugging) of the outermost portion of hair follicles. The cause of this accumulation of keratin is unknown, but it is likely related to an abnormality of keratinocyte differentiation since KP occurs primarily in those who have ichthyosis vulgaris or atopic background. These two conditions are almost always associated with keratinocyte differentiation abnormalities and are especially likely to possess mutations in the filaggrin gene. Histologically, perifollicular lymphohistiocytic inflammation surrounds these keratin plugged follicles.
Management
No therapy is medically necessary. This happenstance is fortunate as no treatment is completely effective. Patients
who are bothered by the appearance or by pruritus may periodically undertake a prolonged bathtub soak followed by the use of light abrasion with a loofah sponge or soft brush. Lubrication, especially with products containing humectants such as urea, lactic acid, or salicylic acid, improves the textural feel of the skin. Topical retinoids, while theoretically attractive as therapeutic agents, tend to increase the inflammation and thus are not routinely useful. In particularly symptomatic or severe cases, laser therapy may be considered.2
who are bothered by the appearance or by pruritus may periodically undertake a prolonged bathtub soak followed by the use of light abrasion with a loofah sponge or soft brush. Lubrication, especially with products containing humectants such as urea, lactic acid, or salicylic acid, improves the textural feel of the skin. Topical retinoids, while theoretically attractive as therapeutic agents, tend to increase the inflammation and thus are not routinely useful. In particularly symptomatic or severe cases, laser therapy may be considered.2
 Fig. 6-4. Although keratosis pilaris sometimes appears inflamed, it is generally asymptomatic. |
KERATOSIS PILARIS Management
20-minute bathtub soak
Light scrubbing with a soft brush or loofah
Application of a moisturizer after the soak and scrub
Cautious trial of topical retinoids
Scabies
The primary discussion of scabies can be found in the section on Pediatric Issues in Chapter 15. Only a few summarizing points will be made here. Scabies generally occurs as a pink or red papular eruption. Characteristically a few linear vesicles or elongated edematous papules (mite burrows) will be present (Fig. 6-5). Dermoscopy can show these burrows with more clarity, and even occasionally show the mite itself. Typically, lesions develop in the digital web spaces, on the volar wrists, and on the elbows. However, the genitalia in males and the mammary area in adult females may be involved. It is an extremely common disorder in poor, underdeveloped countries where its prevalence is estimated at 150-200 million persons. Children are affected most often, but it certainly also occurs in infants and in sexually active adults. In Western countries today, it is most often encountered in the elderly who are housed in congregate living facilities. The most common treatment is with either topical permethrin 5% cream or oral ivermectin in a dose of 200 µg/kg. The nodular form of scabies is discussed with the nodular lesions in Section B of this chapter.
 Fig. 6-5. Scabies most often occurs in skin folds as small oval papules, but sometimes red, excruciatingly pruritic red papules can occur. (Courtesy of Lynette J. Margesson.) |
Miscellaneous Bites and Infestations
The most common bites that occur in the anogenital area are due to chiggers. These “bites” are especially likely to occur at the waistband, in the inguinal folds, and/or on the shaft of the penis. An extensive review has recently been published.3 Chiggers, also called harvest mites, are active during the warmer months when they colonize tall grasses and brush. The larval form of these mites latch onto exposed, nonclothing covered skin of those who contact this greenery. These mite larvae are extremely small, generally requiring magnification to be visualized. Dermoscopy can be useful for this. They then find and settle in folded areas or in spots where clothing tends to bind to the skin. They do not bite in the true sense of the word. Instead, they attach to the skin using their mouth parts, and their saliva liquefies the stratum corneum epidermal cells thus forming a “tube” through which they suck the nourishing fluid, which bathes the lower epidermal cells of the skin. This results in the development extremely pruritic, red, nonscaling, dome-shaped 0.5- to 1.0-cm papules (Figs. 6-6 and 6-7). Often a darker red dot, representing the feeding “tube,” can be seen at the center of the papule. Clustering of multiple papules is usually present and is a distinguishing diagnostic feature for chigger bites.
The mites fall off of the host in 2-4 days, and the papules slowly resolve spontaneously. Oral antihistamines and topical steroids provide some symptomatic improvement of the itching. Prevention of chigger “bites” is the
better part of therapy. This can be achieved through the use of standard insect repellents and the wearing of long sleeves and long pants.
better part of therapy. This can be achieved through the use of standard insect repellents and the wearing of long sleeves and long pants.
 Fig. 6-6. This patient developed red, dome-shaped, nonscaling, pruritic papules around her panty line produced by chiggers after a hike. In general, these are concentrated at the panty line. |
 Fig. 6-7. This woman exhibits poorly demarcated pink, dome-shaped papules of insect bites on the mons and lower abdomen. |
Insect bites in the genital area, other than those due to chiggers, are otherwise uncommon because this area is usually protected by clothing. However, such bites do occur in campers and hikers who expose the genital area when urinating, defecating, or having intercourse alfresco. When these lesions do occur, they also appear as pruritic red papules. Usually only a few papules are present, and when multiple, there is much less likelihood of clustering than with chigger bites. While there is nothing that clinically identifies which insect is responsible for these bites, the likelihood that a given red papule is due to one or another type of insect can be strongly suggested by the presence of numerous eosinophils within the inflammatory infiltrate of a biopsy specimen.
Cherry Angioma
Cherry angiomas (Campbell de Morgan spots) represent a benign neoplasm of clustered capillary blood vessels. They first appear in young adult life and thereafter slowly increase in number with age. These angiomas may be small macules at their inception but fairly quickly develop into sharply marginated dome-shaped papules that are bright red, dusky red, or even violaceous in color4 (Fig. 6-8). They vary in size from nearly flat, pinpoint lesions to 3-or 4-mm papules. The majority of light-skinned persons will have developed at least one by age 40, and the average adult may have 30 or more lesions. It is not that dark-skinned persons have fewer angiomas but rather that they are less easily visible against a darker background. A rare variant, eruptive cherry angiomas, involves the explosive development of 50 or more lesions over a very short period of time. Cherry angiomas are most commonly found on the trunk and proximal extremities but occasionally are also noted on the thighs, buttocks, pubis, and genitalia.4
 Fig. 6-8. Cherry angiomas are bright-red, well demarcated, and best seen in light complexioned individuals. |
The cause of cherry angiomas is not known though the frequency of familial development suggests a genetic predisposition as does the high frequency of GNA, especially GNA14, gene mutations that occur.5 A risk factor for the development of these angiomas is use of the alphaadrenergic receptor blocker, tamsulosin.4 Other possible risk factors include the presence of dyslipidemia, chronic immunosuppression, benign prostatic hypertrophy, and various malignancies. Use of the medication, clopidogrel, may reduce the likelihood of developing these angiomas.4
The diagnosis is made on a clinical basis. The differential diagnosis is that of angiokeratomas. Since both disorders are asymptomatic and benign, it is not always necessary to differentiate between these lesions. No treatment is necessary. Lesions that are troublesome to patients or those that bleed frequently with trauma may be excised or may be destroyed with electrosurgery, cryotherapy, or laser ablation.6
Angiokeratoma
Angiokeratomas commonly occur on the genitalia and consist of clusters of ectatic, superficial cutaneous blood vessels. A recent major review has recently been published.7 These benign papules are sometimes given the eponymous epithet of Fordyce but that name should not be confused with Fordyce spots referring to prominent
sebaceous glands on the lips or genitalia. Angiokeratomas are sufficiently common to be considered as a normal variant rather than a disease. The prevalence is not known, but based on our experience, they develop in early adulthood in about 10% of men but considerably less frequently than that in women. In males, they appear as multiple 1- to 2-mm red, smooth-surfaced, dome-shaped papules occurring primarily on the scrotum and, rarely, on the penile shaft7 (Fig. 6-9). Sometimes they are lined up as tiny (“beads on a string”) outpouchings along a linear telangiectatic vessel (Fig. 6-10). Generally, 10-30 scrotal papules are present. In females, the lesions are found on the vulva, especially the labia majora, where they are fewer in number (often solitary), larger in size (3-8 mm), and darker in color (dusky red, violaceous, or blue) (Figs. 6-11 and 6-12). In both sexes, bleeding with minor trauma sometimes happens, but angiokeratomas are otherwise asymptomatic.
sebaceous glands on the lips or genitalia. Angiokeratomas are sufficiently common to be considered as a normal variant rather than a disease. The prevalence is not known, but based on our experience, they develop in early adulthood in about 10% of men but considerably less frequently than that in women. In males, they appear as multiple 1- to 2-mm red, smooth-surfaced, dome-shaped papules occurring primarily on the scrotum and, rarely, on the penile shaft7 (Fig. 6-9). Sometimes they are lined up as tiny (“beads on a string”) outpouchings along a linear telangiectatic vessel (Fig. 6-10). Generally, 10-30 scrotal papules are present. In females, the lesions are found on the vulva, especially the labia majora, where they are fewer in number (often solitary), larger in size (3-8 mm), and darker in color (dusky red, violaceous, or blue) (Figs. 6-11 and 6-12). In both sexes, bleeding with minor trauma sometimes happens, but angiokeratomas are otherwise asymptomatic.
The diagnosis is made on a clinical basis. In men, the main differential diagnosis is cherry angiomas (Campbell de Morgan spots). Angiokeratomas found in the extremely rare, X-linked condition, angiokeratoma corporis diffusum (Anderson-Fabry disease), are individually similar in appearance, but in this life-threatening systemic disorder, they are much more numerous and occur in wider distribution pattern to include the lower trunk and upper thighs. In women, solitary, darker lesions may be confused with nevi or even melanoma, and for that reason, biopsy is usually necessary. Dermoscopy shows the vascular nature of these lesions when there is any question. Biopsy in men is not usually needed. Histologically, angiokeratomas reveal characteristic, clustered, dilated vessels in the upper dermis. The overlying epidermis is slightly
thickened and elongated rete ridges usually extend into the dermis around the vessels, sometimes entirely encircling them. The cause of these lesions is unknown. However, based on their frequent occurrence along a dilated vessels on the scrotum, it is possible that they develop as saccular varices in aging, weak-walled capillaries.
thickened and elongated rete ridges usually extend into the dermis around the vessels, sometimes entirely encircling them. The cause of these lesions is unknown. However, based on their frequent occurrence along a dilated vessels on the scrotum, it is possible that they develop as saccular varices in aging, weak-walled capillaries.
 Fig. 6-9. Angiokeratomas of the scrotum are typically large in number, and generally dark purple. |
 Fig. 6-10. On the scrotum, angiokeratomas sometimes align along veins resulting in this peculiar beaded pattern. |
 Fig. 6-11. Angiokeratomas of the vulva are more often fewer or even single in number. |
 Fig. 6-12. Sometimes the vulva also displays large numbers of angiokeratomas; these range from very tiny to several millimeters and from bright red to dark purple, almost black. |
SECTION B: RED NODULES
The discussion in this section covers disorders that are primarily nodular. That is, it centers around those disorders wherein the majority of the lesions are 1.5 cm in diameter or even quite a bit larger. However, in some instances, smaller lesions (papules) may be intermingled among the larger nodules.
Hidradenitis Suppurativa (Acne Inversa)
Hidradenitis suppurativa (HS) is a chronic disfiguring disease that is difficult to treat successfully. It is often accompanied by pain, drainage, and odor. As such, it has the potential to materially reduce the quality of life for patients affected by it. Several extensive reviews of this disease have recently been published. These include twopart articles in 2019 and 20208,9,10,11 and another lengthy single article in 2020.12 These publications support nearly all of what is written below, and thus, I will not reference them for each point made.
Clinical Presentation
Hidradenitis suppurativa is a relatively common problem with an estimated prevalence of about 1%-2% in Western countries with a slightly higher rate elsewhere. Similarly, it affects women more often than men in the west, but men develop HS more often, and more severely, elsewhere. With the exception of familial cases, it rarely develops before age 20 and is most commonly encountered during the third and fourth decades of life. New onset after menopause is unusual, and disease activity, whenever it starts, tends to decrease slowly over time. Most clinicians believe that HS is more common in Africans and African Americans, but data to support this supposition are not very persuasive. A positive family history for HS is found in about one-third of the patients. Smoking (current and former), obesity, and a positive family history for HS are notable predisposing factors associated with its development. (See also the section on “Pathophysiology” below.) In a “chicken and egg” sort of way, it is not clear whether the association with “metabolic syndrome” (large waist circumference, abnormally high blood sugar, increased blood pressure, and elevated lipid levels) is a predisposing factor or occurs as a result of having HS. In addition, there are associations with many other medical disorders. These include inflammatory bowel disease, pyoderma gangrenosum, polycystic ovarian syndrome, arteriosclerosis, thyroid dysfunction, and arthropathic disorders. HS can also be encountered in association with severe cystic acne and dissecting cellulitis (noninfectious inflammatory cysts) of the scalp (the follicular retention triad).
The quality of life for patients with HS is very seriously impaired, perhaps more so than for patients with any other common dermatologic disease. Patients are hindered both socially and at work because of odor and drainage. Sexual intimacy becomes impossible for many of those with HS. Some patients are even rejected by the clinicians from whom they seek therapy. Severe psychological disability often occurs, and most patients with moderate to severe disease develop significant anxiety and/or depression. Not surprisingly, there is an increased risk for suicide.
Hidradenitis suppurativa begins with painful, red nodules, many of which eventually rupture and form chronic, draining sinus tracts (Figs. 6-13, 6-14, 6-15, 6-16, 6-17, 6-18, 6-19, 6-20, 6-21). The inflammatory nodules greatly resemble furuncles and are often initially misdiagnosed as such. Chronic ulcers can also develop. Both the sinus tracts and the ulcers tend to heal with thick ropelike scars (Fig. 6-22). In the worst instances, these scars result in contracture formation. Comedones, with black follicular plugs, are regularly found in the areas around the inflammatory lesions (Figs. 6-23 and 6-24). These comedones are larger than normal. The presence of two comedones separated by only 1-2 mm of normal skin (“twin” comedones) is sufficiently distinctive to represent a helpful diagnostic sign of the disorder. The older literature suggested that these “twin” black heads occurred as a result of a bifurcated follicular outlet. More recently, it has been
found that at least in many instances they are pseudocomedones without attached complete hair follicles and that they form as part of the postinflammatory scarring process.13
found that at least in many instances they are pseudocomedones without attached complete hair follicles and that they form as part of the postinflammatory scarring process.13
 Fig. 6-13. Hidradenitis suppurativa ranges from an occasional inflamed cyst, as in this patient, to large numbers of coalescing nodules. |
 Fig. 6-14. As inflamed cysts rupture, they sometimes eventuate into chronic draining sinus tracts, surface erosions, and depressed scarring. |
 Fig. 6-15. Some people experience multiple, mostly discrete, waxing, and waning inflammatory lesions. |
 Fig. 6-16. Other individuals experience coalescing nodules that connect in the subcutaneous tissue, producing deep fibrotic scarring and induration. |
 Fig. 6-17. Hidradenitis suppurativa also can affect the perianal skin and buttocks, so that even sitting is painful. |
 Fig. 6-18. The constant drainage from sinus tracts produces irritant contact dermatitis, odor, and rawness, as occurs in the inguinal fold of this man. |
 Fig. 6-19. The scarring from HS has resulted in hard, nonpitting edema of the scrotum. |
 Fig. 6-20. Red, eroded, exophytic nodules sometimes form at the exit of draining sinus tracts. |
 Fig. 6-21. This woman has constant wetness from her constantly draining HS cysts. |
 Fig. 6-22. HS occurs often in the axillae; this man has severe scarring and constant drainage from one axilla and his buttocks only. |
 Fig. 6-23. Fairly subtle comedones, some “twin comedones,” are characteristic of HS, with careful inspection. |
The inflammatory lesions of HS occur almost solely at sites possessing hair follicles with associated apocrine glands, even though the apocrine glands themselves do not seem to be involved in the direct pathogenesis of the lesions. Because of the relationship between mammary glands and apocrine glands, it is not surprising that nearly all of the lesions of HS occur along the “milk line” that runs from the axillae through the mammary area and extends into the pubic, inguinal, genital, perineal, and perianal area. Scattered lesions (presumably related to ectopically located apocrine gland-related follicles) may be found on the buttocks and thighs. The axillae and buttocks are the locations most often affected in men; the anogenital area and the upper inner thighs are the location most commonly involved in women. Several systems for documenting the severity of HS have been proposed. Of these, the Hurley staging and the Sartorius score are the two most commonly used in clinical studies; neither is often used in clinical day-to-day practice.14
 Fig. 6-24. Occasionally, comedones are quite prominent. |
Diagnosis
A diagnosis of HS is made on a clinical basis.15 The clinical features that lead to the diagnosis include (1) the presence of multiple lesions bilaterally, (2) the location of lesions within the milk line, (3) recurrence of lesions at the same site, (4) long-lasting duration (weeks to months) of individual lesions, (5) bacterial cultures that are either negative or demonstrate a multiplicity of bacterial species, and (6) failure to respond quickly (7-10 days) and completely to antibiotic therapy. Diagnostic algorithms that include many of these features have been proposed. Biopsy is rarely indicated, and because of the nonspecific inflammation that is found, it is usually not helpful if it is carried out. However, when Crohn disease is a consideration, and there is no history of bowel disease, a biopsy may be helpful to separate it from HS.
Two common diseases should be considered in the list of differential diagnoses. First, furunculosis is the condition with which HS is most often confused. Several clinical features are useful in identifying furunculosis: (1) only one or two, rather than multiple, inflammatory nodules are usually present at any one time; (2) lesions are found at random sites rather than mostly within the milk line; (3) culture reveals only a single bacterial species (almost always Staphylococcus aureus); and (4) there is a complete response to appropriate antibiotic therapy within 7-10 days. Second, anogenital cutaneous Crohn disease can look very much like HS. A history of bowel symptoms and signs, the lack of “twin” comedones, absence of lesions outside the anogenital region, the presence of anal fistulae, and the somewhat more distinctive histological findings on biopsy would point toward a diagnosis of Crohn disease. Note, however, that even though they appear to be entirely separate entities, there are several reports indicating that the two diseases coexist with a greater frequency than would be expected by chance. Other disorders that may present with lesions that mimic the inflammatory nodules of HS include deep fungal infections (especially in the immunosuppressed), mycobacterial infections, granuloma inguinale, and inflamed cysts of various types.12
HIDRADENITIS SUPPURATIVA Diagnosis
Multiple lesions are present.
Lesions located within the milk line.
Recurrence of lesions at the same site.
Long duration of individual lesions.
Little or no spontaneous regression of the overall disease.
Cultures sterile or contain multiple species of bacteria.
Slow and incomplete resolution with oral antibiotics.
Pathophysiology
Multiple elements are associated with the development of HS. Some of these include lifestyle factors. A past or currant history of smoking is present in an astoundingly high proportion of patients. Interestingly, cessation of smoking leads to little or no improvement in the patient’s HS. Obesity, with or without features of the complete metabolic syndrome (see above), is also frequently found. This obesity contributes to sweat retention and friction both of which contribute to the development of inflammation. Genetic factors are also important. As indicated above, nearly a third of HS patients have a positive family history of the disorder. It is worth noting that at the molecular level, some Asian patients with familial HS have gamma secretase gene mutations leading to Notch receptor deficiency. These mutations, at least in mice, lead to follicular hyperkeratosis and the development of hair follicle cysts.12,16 Immune factors play a role as well. There is upregulation of interleukin-1β and tumor necrosis factor alpha both of which increase the presence of neutrophils. These neutrophils result in abscess formation with eventual rupture of involved hair follicles and purulent drainage. If this abscess-related necrosis breaks through the skin, secondary bacterial colonization and/or infection may occur. These and other similar abnormalities suggest that HS is part of the autoinflammatory spectrum of disorders and helps to explain its reported association with Crohn disease and pyoderma gangrenosum.12,16
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