Eur. J. Pediat. Dermatol. 26, 25-9, 2016

Managements of the less common paraviral in children – asymmetrical periflexural , papular-purpuric gloves and socks syndrome, eruptive pseudoangiomatosis, and eruptive hypomelanosis

Chuh A.1, Fölster-Holst R.2, Zawar V.3 1School of Public Health and Primary Care, The Chinese University of Hong Kong and Prince of Wales Hospital, Shatin, Hong Kong 2Universitätsklinikum Schleswig-Holstein, Campus Kiel, Dermatologie, Venerologie und Allergologie, Germany 3Department of Dermatology, Godavari Foundation Medical College and Research Center, DUPMCJ, India

Summary Although all paraviral exanthems in children are self-remitting, clinicians should be awa- re of the underlying viral leading to complications. Many reports covered the commonest paraviral exanthems, namely pityriasis rosea and Gianotti-Crosti syndrome. We reviewed here the managements of the less common paraviral exanthems in children. For asymmetrical periflexural exanthem/unilateral laterothoracic exanthem treatments should be tailored to the stages of the rash. For children with papular purpuric gloves and socks syndrome, important differential diagnoses such as Kawasaki disease should be ex- cluded. Where this exanthem is related to , the risk of aplastic reticulocytopenia should be monitored for. Clinicians should also be aware of ongoing in- fectivity of parvovirus B19 infection upon rash eruption, and possible exposure to pregnant women. For children with eruptive pseudoangiomatosis, important differential diagnoses should be excluded. For eruptive hypomelanosis, the prime concern is that virological investiga- tions should be contemplated where available, as there exists only clinical and epidemiolo- gical evidence for this novel exanthem being caused by an infectious microbe.

Key words Acyclovir, Gianotti-Crosti syndrome, human herpesvirus-7, human herpesvirus-6, papu- lar acrodermatitis, pityriasis rosea.

araviral exanthems (PE) are skin eruptions 2015), with the latter nomenclature likely to be suspected to be caused by viruses (26). The more appropriate owing to the valid description commonest PE are pityriasis rosea (PR), of the rash distribution (Bodemer C., personal Gianotti-CrostiP syndrome (GCS, also known as communication, 2015). Currently, many investi- papular acrodermatitis of childhood), asymme- gators and clinicians believe that APE and ULE tric periflexural exanthem (APE) (29), unilateral are synonyms. Unilateral mediothoracic exan- laterothoracic exanthem (ULE) (5, 6), papular- them (UME) is likely to be a rare variant of ULE purpuric gloves and socks syndrome (PPGSS) owing to clinical manifestations and lesional hi- (25), eruptive pseudoangiomatosis (EP) (7), and stopathological changes (10, 16). EH is a novel eruptive hypomelanosis (EH) (9, 11, 30). paraviral exanthem (9, 11, 30). APE could be the same or a very similar dise- Reports are proliferating for the manage- ase as ULE (Taïeb A., personal communication, ments of PR and GCS. It is usually considered

25 Chuh et Al. that the management of the other PE would be cage. It is very difficult to diagnose APE/ULE in only symptomatic relief, while waiting for spon- this stage. When it has been diagnosed, the main- taneous remission. Important management para- stay of treatment are potent anti-pruritic measu- meters can be omitted. In this article, we hope res, such as topical mometasone counting on its to cover the non-generic aspects on the manage- anti-inflammatory effects (4). ments of the less common PE. In the second “coalescence stage” (5, 6, 29), lesions are spreading out to the trunk and proxi- mal aspect of the unilateral upper and lower ex- Asymmetric periflexural exanthem / unila- tremities. The primary lesions would have turned teral laterothoracic exanthem brownish, for which no treatment might be ne- cessary. Topical mometasone could be applied to ULE (5, 6), APE (29), and their rare variant the new lesions. UME (10, 16) are likely to be the same or very During the third “regression stage” (5, 6, 29), similar exanthems. Almost all of the 300 reported previous lesions are brownish. Moisturisers as patients were young children. Up to now, only 12 lotions could be applied to the trunk and limbs, adult patients with APE/ULE/UME have been re- sparing the unilateral axilla and the unilateral in- ported (23). guinal crease in the parts of the world with high Typical lesions in APE/ULE are small erythe- relative humidity to prevent intertrigo. matous papules with hypopigmented peri-lesio- Scales appear in the final “desquamation sta- nal halos. The larger lesions are macules, scaly, ge”. Emollients as creams would be appropriate. or coalescent plaques. The eruption usually starts If the local weather is dry, ointment might be in- near one axillary region, spreading centrifugally, dicated, again sparing the flexures. then becoming more widespread (29), and final- ly remits spontaneously in around four weeks (5, 29). Papular-purpuric gloves and socks syndrome APE/ULE is often associated with Epstein Barr virus and parvovirus B19 infections (22). Other PPGSS can occur in infants, children and associated viruses include parainfluenza viruses adults. It is typically preceded by fever, fatigue, and adenoviruses. and coryzal symptoms. Hands and feet of the The differential diagnoses of APE/ULE depend patient then become erythematous and swollen. on the geographical location of the child and the A sharp demarcation at the levels of gloves and background incidence of other dermatological di- socks is characteristic (25). Lesions in PPGSS seases. Prominent differential diagnoses include are usually pruritic, and sometimes painful (28). atopic dermatitis, allergic contact dermatitis, drug Satellite lesions over the more proximal regions eruptions, unilateral blaschkitis (3), PR, GCS, of limbs are common. Spontaneous remission oc- papular urticaria, miliaria, (21), and curs two to four weeks after rash onset. ectoparasitic infestations. The initial asymmetric PPGSS is particularly associated with parvovi- monomorphous papules and the subsequent cli- rus B19 infection (24, 27, 28). Other associated nical stages in otherwise healthy children are the viruses include , coxsackie vi- major diagnostic clues to APE/ULE. rus, hepatitis , HIV, and virus. In the experience of the authors, most children Differential diagnoses of PPGSS include ri- with APE/ULS are asymptomatic, and no inter- ckettsial diseases, hand-foot-mouth disease, Ka- vention of any kind is necessary. When treatment wasaki disease, serum sickness, GCS, and hand- is warranted, the non-generic aspect is that dif- foot syndrome due to chemotherapy. The course ferent treatments might be indicated for its four of the disease and the sharp demarcation of the overlapping stages (5, 6, 29). erythema at gloves and socks levels will substan- After a coryzal prodrome, the first “eczema- tiate the diagnosis of PPGSS. tous stage” debuts as erythematous papules at There exists three particularly non-generic unilateral axilla and the adjacent lateral thoracic aspects of managing children with PPGSS. The

26 Managements of the less common paraviral exanthems in children first is that for children with congenital hemoglo- later, as monomorphous erythematous papules of binopathies and PPGSS due to parvovirus B19 around 2.5 mm in size, on the face, trunk, and infection, complete blood count should be mo- the four extremities. Telangiectasia can be seen nitored to detect aplastic reticulocytopenia at an on close observation or via an epiluminescence early stage of this complication. dermatoscope. Lesions are blanchable, and are The second non-generic aspect is that PPGSS sometimes surrounded by hypopigmented halos. can be very acute with high fever and fatigue. Spontaneous remission then occurs around four Investigations would be necessary to exclude its weeks after rash onset. differential diagnoses, the commonest ones being The initial patients reported by Cherry et Al. hand-foot-mouth disease and Kawasaki disease. (7), were associated with echovirus infections. Signs of Kawasaki disease should be actively However, evidence of such infections was not looked for in these children. In this phase, anti- found in subsequent children with EP. pyretics can be prescribed for the symptomatic EP causes almost no complication in children. remission. Some of the larger lesions may burst upon physi- In the next stage, hands and feet would beco- cal pressure, leading to bleeding. me swollen with erythema. However, for some The non-generic aspect of the management of patients, swollen hands and feet appear concomi- EP lies in its diagnosis. It is very easily missed tantly with the febrile and fatigue phase. Pruritus with its differential diagnoses including spider over the hands and feet is the rule, and can be nevi, cherry angiomas, multiple pyogenic granu- alleviated with systemic histamine-antagonists lomas, and bacillary angiomatosis. such as chlorpheniramine or loratidine. We have The course of the exanthem and the blanchable found that topical calamine lotion to be applied monomorphous papules would suggest the dia- to the hands and feet would be fit complements to gnosis being EP. the oral anti-histamine treatments for most chil- dren with PPGSS. In this stage, pain can be severe for children. Eruptive hypomelanosis Systemic paracetamol would be adequate. Non- steroidal anti-inflammatory agents might not be EH is a novel paraviral exanthem (9, 11, 30). necessary. The use of aspirin should particularly Most reported patients are young children be- be avoided to minimize the risk of Reye syndro- low the age of six. After a prodromal coryzal me. stage, monomorphous hypopigmented macules The third non-generic aspect of management is of around 2-5 mm would be seen mainly on the one of infectivity. For erythema infectiosum, the extensor surface of the limbs. Systemic involve- infectivity of parvovirus B19 is very low once the ment including pharyngitis and lymphadenitis is erythematous cheeks and reticular lesions on the common. trunk are seen in children. However, this is not This exanthem is usually asymptomatic. The the case for PPGSS, with the children still being prime concern is to perform virological investi- infectious when the skin rash appears. Therefore, gations where available, as virus has been not yet arrangements for isolation and contact tracing for identified as the cause of EH. pregnant women, as parvovirus B19 infection in pregnancy could lead to severe fetal , non- autoimmune fetal hydrops, and miscarriage. Discussion

Investigations on the treatment of PR in chil- Eruptive pseudoangiomatosis dren and in adults have been dynamic over the past two decades, because of several factors. Most patients with EP are children. They ex- Firstly, much virological evidence was reported perience a prodrome of fever, fatigue, or mild on the association of PR and human herpesvirus diarrhea. The eruption appears four to seven days (HHV)-7 and -6 (HHV-6) infections, particularly

27 Chuh et Al. endogenous reactivation of HHV-7 (18, 19). This employing antibiotics for anti-bacterial action. led to a series of clinical trials evaluating the ef- We have previously shown that PR is highly ficacy of low-dose and high-dose oral acyclovir unlikely to be associated with Chlamydia pneu- to treat PR (20). Secondly, there was an initial moniae, C. trachomatis, Legionella longbeachae, enthusiasm on the efficacy of oral erythromycin L. micdadei, L. pneumophila, and Mycoplasma in treating PR. This led to subsequent trials on pneumoniae infections (12), which are likely to the use of newer macrolides such as azithromycin be sensitive to macrolides. In the case of any and clarithromycin to treat PR (1, 2). modification on the course of PR, such changes Thirdly, it was reported that the rash severity are likely to be related to the anti-inflammatory of PR is not closely correlated with impacts of and immuno-modulating effects of the macrolide PR on the quality of life (QOL) of patients (15) concerned. and that most patients with PR might not need Along similar paths, it was known decades any treatment (13). This is particularly true for ago that HHV-6 and HHV-7 lack thymidine ki- children, for whom PR (14) and GCS (8) exert nase for the phosphorylation of acyclovir, and little impact on their QOL. would not be particularly sensitive to acyclovir These findings might apply to less common PE (17). Whether acyclovir, or other antiviral agents, as well. Virological investigations are of course is effective on PR or other exanthems related to necessary for these PE. Although severe compli- HHV-6 or -7 should be determined by results in cations are not observable at the present stage of clinical trials. knowledge, the underlying viral infections could As aforementioned, PE casts low impacts for stay as lifelong latent infections, and could mani- children as PR (14) and GCS (8). Clinical trials fest complications decades later when the hosts to establish efficacies of specific treatment moda- become immunocompromised. Furthermore, the lities might not be warranted in the current stage gravity of chromosomal integration of HHV-6 or of knowledge. other viruses is yet to be assessed. We have thus highlighted the most prominent Treatments of these exanthems are unlikely non-generic aspects in the management of the- to be a straightforward find-cause-and-treat-the- se PE. We hope that future studies on these less cause. common PE would be based on patient-assessed The efficacy, or lack of efficacy, of erythromy- outcomes, and that non-generic aspects of mana- cin and other macrolide in PR did not originate gement of these less common PE would be ad- from hypotheses on bacteria causing PR, then dressed.

Address to: Dr Antonio Chuh Shops 5 and 6, The Imperial Terrace 356 Queen’s Road West, G/F Hong Kong Telephone: 852-25590420 Facsimile: 852-22394009 Email: [email protected]

28 Managements of the less common paraviral exanthems in children

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