Robin   Carder

 Atypical viral exanthems: 
  New rashes and variations on old themes 

By K. Robin Carder, MD, and William L. Weston, MD 

A viral skin eruption that doesn't follow a familiar   or classic pattern can confuse the diagnosis, leading to unnecessary tests when   only reassurance is needed. This practical guide to recently identified, less   known, and atypical viral rashes of childhood takes the mystery out of your   evaluation. 

 Viral skin eruptions are familiar to pediatricians and dermatologists alike.   Yet such eruptions can be a source of great confusion. 

 Consider the child who is brought to you with a "rash." She (or he) may have   a concurrent fever or other nonspecific symptoms such as an upper respiratory   infection, sore throat, malaise, or lymphadenopathy. Or she may have only the   rash without a history of associated illness. As clinicians, we are accustomed   to and comfortable with certain patterns. We easily recognize an eruptive, pink,   papular rash following a high fever as roseola or exanthem subitum. Red, "slapped"   cheeks followed by a reticulate erythema on the extremities suggest erythema   infectiosum (fifth disease). We would still recognize red macules and distinct   pink-red papules in a child with high fever, coryza, and conjunctivitis as measles,   even though effective vaccination has made measles uncommon. 

 But it is the eruption that does not follow a recognized or classic pattern   that makes us uncomfortable. Sometimes an eruption follows a classic patternbut   the child is the wrong age. At other times, the lesions look familiar, but their   distribution is unusualthey appear on only one side of the body, for example. 

 We examine the child with the unfamiliar eruption and try to assemble the   pieces of the puzzle, aware that the parents are concerned and looking to us   for help, reassurance, and a diagnosis. We think through a differential diagnosis,   but it raises more questions than answers. Should we order laboratory studies?   Perform a skin biopsy? Prescribe antibiotics or a topical steroid? 

 The goal of this review is to remove some of the mystery from the evaluation   of viral eruptions. Realizing that most diagnostic dilemmas do not involve more   common eruptions, we focus on recently identified and less-known viral skin   conditions (Table 1). We also consider unusual or atypical presentations of   more familiar viral eruptions. We describe the clinical signs and symptoms of   each condition, review helpful laboratory or histologic studies, and, most important,   offer a differential diagnosis to help distinguish between similar eruptions. 

Asymmetric periflexural exanthem of childhood (APEC)       

 Papular-purpuric gloves-and-socks syndrome       

 Atypical pityriasis rosea 
          Inverse 
          Vesicular 
          Purpuric, erythema multiforme-like, urticarial       

 Infectious mononucleosis in toddlers    

 Asymmetric periflexural exanthem of childhood 

 Taïeb and colleagues first described asymmetric periflexural exanthem   of childhood (APEC), also called unilateral laterothoracic exanthem, in 1986   (Table 2).

 Two published case series have evaluated the characteristics   of this eruption.

 Both found a female predominance. The condition   also appears to be seasonal, with peak occurrence in the spring. As the name   implies, the exanthem affects young children, between 1 and 4 years of age,   with a mean age of onset of 2 years. Interestingly, two familial cases have   been described.

Asymmetric periflexural exanthem of childhood 

 Progression of skin lesions is typical 


 Unilateral erythematous papular eruptions near         the axilla 

 Centrifugal spread, morbilliform or eczematous,         asymmetric 

 Variable constitutional symptoms 
          Regional lymphadenopathy 
          Pruritus 
          Fever 
          Rhinopharyngitis, diarrhea, vomiting, otitis       

 Spontaneous resolution in 3­6 wk       

 No treatment available; antibiotics and topical steroids are not helpful       

 The initial eruption is strikingly unilateral. Classically, a pink-red papular   eruption appears first in the area of the axilla, on one side of the body only   (Figure 1); the left side was affected more often in one series.

   Less often, the lesions appear first on the thigh, flank, or inguinal fold.   The palms, soles, and face are always spared. Occasionally, the lesions are   serpiginous (circinate) with central blue-gray coloration. 

 By the end of the first week, the eruption spreads centrifugally, away from   the axilla, and may become bilateral or generalized. Despite the spread, the   papules remain asymmetric with greater involvement of the originally affected   side. After the first week, the lesions may appear more scarlatiniform, morbilliform,   or eczematous. By the third week, the pink-red lesions resolve, leaving only   residual dry skin at week four. The eruption resolves spontaneously in three   to six weeks in most cases, although one case was reported to have persisted   for four months.

 No lasting sequelae have been reported after the   lesions resolve. 

 Most children are otherwise asymptomatic, although half may experience mild   or moderate itching. Localized lymphadenopathy may develop in the area where   the eruption began. Some children have fever, sore throat, otitis, vomiting,   or diarrhea at or near the time of the eruption. 

 The cause of APEC remains unknown. A viral etiology has been suggested because   of the young age group, seasonal occurrence, reports of familial involvement,   and occasional lymphadenopathy and fever.

In the two case series,   laboratory tests did not show evidence of infection. Tests performed included   complete blood cell count, liver function tests, throat cultures, and tests   for Epstein-Barr virus (EBV), cytomegalovirus (CMV), parvovirus B19, hepatitis,   coxsackievirus, 

   (one case tested positive with a low titer

 Skin biopsy findings are nonspecific. Histology reveals only epidermal spongiosis,   exocytosis of mononuclear cells, and perivascular and periappendageal inflammation.

   Because laboratory and histologic studies are nonspecific, diagnosis is based   on clinical findings alone. 

 Although oral antibiotics and topical steroids have been given to treat APEC,   they do not appear to alter the course of the illness.

 In both   case series mentioned, the time to resolution of lesions in treated and untreated   children did not vary. Therefore, no treatment is indicated other than, perhaps,   an oral antihistamine to relieve itching. 

 The unilateral onset of this eruption is unique. Eczematous conditions, such   as allergic contact dermatitis or atopic dermatitis, can be unilateral, but   they are much more pruritic, often weep or crust, and respond well to topical   steroid therapy. The more morbilliform lesions of APEC may mimic miliaria, Gianotti-   Crosti syndrome, or roseola, but differ in their unilateral distribution. Also,   miliaria typically occurs on the face, an area spared by APEC. Gianotti-Crosti   syndrome is localized to the face and extremities, whereas roseola is more generalized   and transient (often fading within 24 hours). APEC also may mimic pityriasis   rosea, but pityriasis rosea occurs more often in older children, is often preceded   by a "herald" patch, and has larger, symmetrically distributed lesions that   follow skin folds. 

 The self-resolving eruption of Gianotti-Crosti syndrome (Table 3) was first   described by Gianotti in Italy in 1955. Soon thereafter, he described an association   between the syndrome and hepatitis B infection. Gianotti defined the association   of the classic skin eruption with hepatitis B infection as true Gianotti- Crosti   syndrome or papular acrodermatitis of childhood.

Etiology is a viral infection (see Table 4) or sequela of vaccination       

 More common in spring, early summer       

 Skin eruptions 
          Flat-topped, red-to-purpuric papules and papulovesicles 
          Symmetric on face, buttocks, extensors (elbows and knees)       

 Variable constitutional symptoms 
          Lymphadenopathy (axillary, inguinal) 
          Low-grade fever 
          Pruritus (uncommon)       

 Spontaneous resolution in 3 or 4 wk       

 Laboratory findings 
          Transient elevation of hepatic enzymes (if patient is hepatitis         B­positive) 
          Evaluation to determine infectious cause       

 Treatment is symptomatic (oral antihistamine for pruritus)       

 Similar cases were later described after infection with nonhepatitis viruses   and were termed papulovesicular acrolocated syndrome because they were thought   to differ clinically from classic Gianotti- Crosti. The clinical findings associated   with hepatitis B infection have since been shown not to differ significantly   from those that follow infection with other viruses.

 Most people   now believe that all such cases should be designated as Gianotti-Crosti syndrome.

 Gianotti-Crosti syndrome is typically a disease of young children. Caputo   and colleagues reviewed more than 300 cases and found the mean age of onset   to be 2 years (range, 6 months to 14 years).

 They also found that   the condition was somewhat more common in boys and during the spring and early   summer. 

 Onset is characterized by the appearance of monomorphous, 2- to 5-mm, red   to red-brown, flat-topped papules (Figure 2). Lesions may also be flesh-colored   or papulovesicular (blister-like papules). Occasionally, they appear purpuric   on the lower extremities or edematous. The papules are distributed symmetrically   on the face, buttocks, and extensor extremities (especially the cheeks, ears,   elbows, and knees). The eruption typically begins on the legs and buttocks,   then spreads upward toward the face within the first week. The flexor surfaces   of the extremities and trunk are usually spared. Occasionally, the lesions are   more widespread but remain dense on the extensor surfaces. Some lesions may   demonstrate the Koebner phenomenon (accentuation in areas of trauma) early in   the course of the eruption. 

 The eruption resolves spontaneously over three to four weeks with residual   desquamation, but may persist for as long as two months.

 Variable constitutional symptoms may accompany Gianotti-Crosti syndrome. In   one series, nonspecific viral symptoms such as fever, cough, rhinitis, and other   upper respiratory tract symptoms preceded the eruption in six of seven cases.

   Lymphadenopathy, especially axillary and inguinal, occurred in approximately   half of the children, and splenomegaly was noted in two (one of whom was the   child who did not have viral symptoms). Each of the seven children had at least   one associated sign or symptom. Hepatomegaly is noted more often in hepatitis   B­associated cases, but more serious hepatitis-related sequelae seldom   occur.

 The association of Gianotti- Crosti syndrome with hepatitis B virus is strongest   in Italy and Japan and most often involves the 

 subtype of the virus;   less often, the 

 Hofmann   and colleagues detected hepatitis B virus in none of seven affected patients   in Germany, but found evidence of EBV virus in five of them.

 No   clear viral etiology was found in the remaining two patients, but both had received   immunizations (polio and DTP plus polio) two to three weeks before onset of   the eruption. Several viral and bacterial infections and several immunizations   have been implicated in the etiology of Gianotti-Crosti syndrome (Table 4).   In Europe and North America, EBV appears to be most often associated with Gianotti-   Crosti.

 Associations with Gianotti-Crosti syndrome 

 Adenovirus 
        Coxsackievirus 
        Cytomegalovirus 
        Echovirus 
        Enterovirus 
        Epstein-Barr virus (most common) 
        Hepatitis A, B, and C 
        Human immunodeficiency virus 
        Parainfluenza virus 
        Parvovirus B19 
        Poliovirus 
        Respiratory syncytial virus 
        Rotavirus 
        Rubella       


        Mycobacterium avium-intracellulare

Diphtheria 
        Influenza 
        Pertussis 
        Polio 
        Tetanus 
        Vaccinia       

 Laboratory findings are not characteristic, with the exception of transiently   elevated levels of hepatic enzymes in cases associated with hepatitis B virus.   Because hepatitis B­ induced cases are rare outside Italy and Japan, possibly   as a result of early vaccination, evaluation for hepatitis B is often unnecessary.   Reserve testing of the hepatitis B surface antigen level for patients with a   history of hepatitis B exposure, systemic symptoms (hepatomegaly, splenomegaly,   diarrhea), elevated hepatic enzyme levels, or Italian or Japanese heritage.   If lymphadenopathy, fever, or sore throat is present, testing for EBV, which   is more likely to be the causative agent in Europe and North America, is recommended. 

 Biopsy is unwarranted because the histopathology of Gianotti-Crosti syndrome   is nonspecific. Findings include hyperkeratosis, acanthosis, and focal parakeratosis   of the epidermis. Perivascular inflammation can be seen in the superficial dermis.

 The distribution and appearance of lesions in Gianotti-Crosti syndrome are   characteristic, and the diagnosis is largely clinical. The lesions, when purpuric,   may occasionally be confused with those of Henoch-Schönlein purpura. In   Henoch-Schönlein purpura, however, the lesions typically do not involve   the face and arms, and gastrointestinal, renal, and joint symptoms are often   present. 

 Lichenoid eruptions also may resemble those of Gianotti-Crosti syndrome. The   lesions of lichenoid drug eruptions tend to occur on areas exposed to the sun,   however, and are uncommon on the buttocks. They also persist until the offending   medication is discontinued (see "

".).   Pityriasis lichenoides et varioliformis acuta (PLEVA) is characterized by recurrent   crops of crusted lesions over weeks to monthsunlike Gianotti-Crosti, in   which lesions are not crusted and resolve within one month without recurrence. 

 As with asymmetric periflexural exanthem, treatment of Gianotti- Crosti syndrome   is indicated only if the child is symptomatic. Oral antihistamines relieve itching;   topical steroids also have been used to control itching but do not usually improve   the appearance of the skin or shorten the duration of the skin lesions.

   In fact, topical steroids occasionally exacerbate the eruption, causing an abrupt   increase in the number of skin lesions.

 For this reason, steroids   are generally discouraged. 

 If hepatitis B virus or EBV is present, precautions should be taken to prevent   spread of infection. Obtain a history of the patient's contacts, and, if indicated,   evaluate them for evidence of infection. 

 Papular-purpuric gloves- and-socks syndrome 

 Also known as petechial glove-and-sock syndrome, papular-purpuric gloves-and-socks   syndrome (Table 5) was first described by Harms and colleagues in 1990.

   They reported a distinct pruritic, erythematous, petechial eruption of the hands   and feet that appeared suddenly, then spontaneously regressed within days of   onset. Since then, many more cases have been reported. 

Papular-purpuric gloves-and-socks syndrome 

Etiology is a viral infection (parvovirus B19)       

 Most often affects Caucasian children and young adults (9­45 yr),         male and female       

 Skin eruption 
          Pruritic or tender erythema and edema of hands and feet 
          Progression to confluent petechiae (palmoplantar and dorsal         surfaces) 
          Sharp demarcation at wrists and ankles 
          Enanthem (petechiae, aphthae, erosions, edema, vesicles) 
          Occasional lesions of face, buttocks, extremities, groin,         trunk       

 Variable constitutional symptoms 
          Lymphadenopathy 
          Transient fever (to 39° C) 
          Arthritis, arthralgia
          Anorexia or myalgia 
          Respiratory or gastrointestinal symptoms       

 Spontaneous resolution in 1­2 wk       

 Laboratory results 
          Anemia, leukopenia, or thrombocytopenia 
          Elevated AST 
          Determine viral cause 
            Presence of parvovirus B19 IgM or IgG antibodies         
            Polymerase chain reaction of skin or serum for         parvovirus B19 DNA       

 Children and young adults (9 to 45 years of age) are affected most often,

   although the eruption has been reported in children as young as 22 months.

   Most cases involve Caucasians, males and females, and tend to occur in the spring   and summer.

 The typical presentation begins with a progressive redness and swelling of   the hands and feet,

 often accompanied by itching or tenderness.   Onset is sudden and redness is strikingly symmetric. The eruption progresses   to numerous, confluent petechiae on the palmoplantar and dorsal surfaces of   the hands and feet over the first few days (Figure 3). A characteristically   sharp demarcation at the ankles and wrists can be noted. Often, petechial or   purpuric lesions appear on the trunk, extremities (especially the inner aspect   of the thighs), groin, genitalia, and face. A characteristic enanthemerosions,   vesicles, petechiae, diffuse redness, edema, or aphthaemay occur on the   oral mucosa, including the tongue, lips, and palate. The cutaneous lesions resolve   spontaneously in one or two weeks with only residual fine desquamation on affected   areas. 

Articles

This practical guide to recently identified, less known, and atypical viral rashes of childhood takes the mystery out of your evaluation.

Robin Carder

Articles

Atypical viral exanthems: New rashes and variations on old themes