|Year : 2015 | Volume
| Issue : 1 | Page : 9-16
Clinicoepidemiological study of vesiculobullous disorders in pediatric age group
Department of Skin and VD, SGT Medical College and Research Institute, Budhera, Gurgaon, Haryana, India
|Date of Web Publication||16-Jan-2015|
H. No. 656, Sector 4, Urban Estate, Gurgaon 122 001, Haryana
Source of Support: None, Conflict of Interest: None
Background: Bullous disorders are a complex group of disorders which continue to be an enigma and a challenge to the medical profession in general and the dermatologists and pediatricians in particular. Due to the delicacy of child's skin, factors of immunobiological response and many other extrinsic and intrinsic factors, the clinical manifestations of cutaneous disorders in children often differs from those in adults.
Aim: The present study aims to know the clinical pattern and to assess the observations as a diagnostic means to detect different vesiculobullous disorders and to find out their prevalence in that age group.
Materials and Methods: The study group comprises children in age group between 0 and 14 years, presenting with intact blisters attending the Skin and VD outpatient Department, SCB Medical College and Hospital, Cuttack and the cases referred from the Department of Medicine and Surgery. All cases were evaluated by means of standard proforma which included a detailed history, thorough clinical examination with appropriate investigations where ever required.
Results: Overall male:female incidence was 3:2. Children in the age group of 1-6 years showed maximum incidence (48/100) of the vesiculobullous diseases, Impetigo being the most common vesiculobullous disease with the highest incidence of 42%. Chronic bullous disease of childhood (CBDC) came out to be the most common immunobullous disease with the incidence of 7% closely followed by dermatitis herpetiformis (DH) (6%). Mucosal involvement was predominantly seen in pemphigus vulgaris, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), while other diseases presented with either skin or both skin and mucous membrane involvement. Lesions in herpes simplex were seen confined to the face. Varicella, herpes simplex, CBDC and DH presented with tense blisters whereas pemphigus group, SJS, and TEN presented with flaccid lesions, with raw areas and crusting seen in all the diseases. Toxic features were encountered in varicella, pemphigus, TEN.
Keywords: Impetigo, pediatric, pruritus, vesiculobullous
|How to cite this article:|
Gupta V. Clinicoepidemiological study of vesiculobullous disorders in pediatric age group. Indian J Paediatr Dermatol 2015;16:9-16
|How to cite this URL:|
Gupta V. Clinicoepidemiological study of vesiculobullous disorders in pediatric age group. Indian J Paediatr Dermatol [serial online] 2015 [cited 2019 Dec 7];16:9-16. Available from: http://www.ijpd.in/text.asp?2015/16/1/9/149402
| Introduction|| |
The field of pediatric dermatology has gained significant recognition in the past several years.  Skin diseases in childhood are common and may constitute at least 30% of all outpatient visits to pediatricians and 30% of all visits to a dermatologist involve children. 
In infants and children, the diagnosis of skin diseases is based on evaluation of same factors as used in diagnosing adult cases. There are two additional factors that must be taken into consideration when dealing with younger patients: (a) Tendency for younger skin to react sometimes differently than adult skin and (b) Lack of first-hand history from new born and older infants because of which purely objective evaluation becomes much more important in these patients. Child's skin is quite different from adult's skin. Anatomically, it is thinner, less cornified and less hairy with physiologically lesser sweat and sebaceous gland secretions. Physically it is more permeable and immunologically less developed. Thus, so far as the skin is concerned, "the child is not just a little man". 
The morphology of the lesion often provides a visual clue to its location as the blisters localized to the epidermal layers are thin walled and flaccid and tend to rupture easily, while the blisters located sub-epidermal are thick walled and more durable.
Blistering disorders are a heterogeneous group of dermatological disorders. In most cases blistering (vesicles and bullae) is due to primary disease, for example, pemphigus. It may also occur as a secondary phenomenon in a number of unrelated conditions. In many cases, bullous diseases cannot be differentiated clinically and needs the help of histopathological examination and immunofluorescence (IMF) study. Routine histological examination can help in the diagnosis of most of the blistering cases according to location and morphology of blisters. Most immune mediated blistering diseases can be defined on the basis of IMF findings, and the pattern is often diagnostic. Blistering diseases can broadly be separated into inherited, autoimmune, infective, and miscellaneous types. 
Amongst the inherited disorders epidermolysis bullosa (EB), porphyria cutanea tarda (PCT), congenital icthyosiform erythroderma, incontinentia pigmenti, some diseases like junctional and dystrophic forms of EB can prove to be fatal in some and can lead to permanent disability in others. Among the autoimmune disorders are included, linear IgA dermatosis or chronic bullous disease of childhood (CBDC), dermatitis herpetiformis (DH), pemphigus, pemphigoid, epidermolysis bullosa aquisita (EBA), and bullous systemic lupus erythematosus. Various infections can also lead to blistering and the most common being bullous impetigo among the bacterial causes. Other common infections that may present with vesicles and bullae are herpes, candidiasis, congenital syphilis and scabies. Among the miscellaneous group comes the rare conditions like Stevens-Johnson syndrome More Details (SJS)/toxic epidermal necrolysis (TEN), transient acantholytic dermatosis, eczema, insect bites, trauma, acute contact dermatitis, erythema multiforme, and miliaria crystallina. Most of these disorders are exceedingly rare in pediatric age group. Thus, when they do occur, there is often a delay in making a correct diagnosis. 
The inherited blistering disorders, though uncommon have a dramatic impact on patient and their family. The most common being the EB group of disorders which are genetically determined skin fragility disorders characterized by blistering of skin and mucosa following mild trauma and hence given alternate term mechanobullous disorders.  The clinical features in older children and adults are fairly distinctive, but it is usually not possible to make a definite diagnosis of a specific type without taking lab investigations. The treatment of all forms of EB is supportive. DNA based prenatal diagnosis is available for junctional and dystrophic forms of EB in families in which there is a known history of EB and ideally in whom the mutation has been characterized. Gene therapy remains the future hope for treatment of EB. 
Autoimmune blistering disorders are exceedingly rare in children. In most cases, they are characterized by circulating antibodies directed against adhesion structures of the skin which subsequently induce blistering at dermoepidermal junction or intraepidermally. The most frequent immunobullous disease in pediatric age group is linear IgA dermatosis, all others DH, pemphigus, pemphigoid, EBA are less common than in adults.  IMF can demonstrate the antibodies bound in the skin or antibodies circulating in the serum by showing specific green fluorescence under the fluorescent microscope. Mainstay of treatment of this group is steroids, usually in high doses either oral or i/v.
A number of cutaneous infections can commonly present with blistering in childhood, most common being impetigo, herpes and a few like scabies and congenital syphilis may have vesicular lesions which is never a feature in adults.
Authors such as Duhring,  Civatte,  Lever,  Lyell,  Nikolsky  Tzanck,  Auspitz  were the first to make original and valuable contributions in the field of vesiculobullous disorders.
Only limited information is available about frequency of specific skin diseases in children and due to the rare incidence of each of these diseases in children, most of the cases have been reported as case reports and there are no previous studies regarding the pattern of vesiculobullous diseases exclusively in pediatric age group. The present study is an attempt to throw some light on the incidence of these diseases in children. It also aims to assess the observations as a diagnostic means to detect different vesiculobullous disorders and to find out their prevalence in that age group.
The present study consists of observation of 100 cases of vesiculobullous disorders in children between 0 and 14 years of age group, with an idea to know their clinical pattern. It also aims to assess the observations as a diagnostic means to detect different vesiculobullous disorders and to find out their prevalence in that age group.
The importance of reaching at a correct diagnosis lies in the fact that few of these disorders like EB group of disorders and various immunobullous disorders can lead to permanent disability and can even prove to be fatal, if not diagnosed at an early stage and managed appropriately.
| MATERIALS AND Methods|| |
The present study was undertaken in the Department of Skin and VD, SCB Medical College, Cuttack.
The study group comprises patients attending the Skin and VD outpatient department, SCB Medical College and Hospital, Cuttack during the period of August '07 to October '09, and the cases referred from the Department of Medicine, Surgery, and Oncology. Selection was on the basis of following criteria:
- Inclusion criteria: Only children between age group of 0-14 years, presenting with intact blisters, both sexes, parent/guardian giving verbal consent for the study
- Exclusion criteria: Children treated outside this referral hospital were not included in this study.
All the cases were subjected to a thorough history taking including name, age, sex, address, religion, economic status of the family along with chief complaints, total duration of disease, related past, family and treatment history, complete general physical, local, and systemic (where necessary) examination.
Routine investigations were carried out in all the cases, while special investigations like Tzanck smear (cytology), bacterial smear and culture, histopathological examination and IMF study was restricted to only few cases where they carried diagnostic importance.
| Results|| |
A total of 17 vesiculobullous diseases were detected in the present study comprising a total of 100 patients. The observed series consists of 42 cases of impetigo, 7 varicella, 2 herpes simplex, 6 bullous scabies, 7 CBDC, 6 DH, 1 pemphigus foliaceus (p. foliaceus), 1 pemphigus vulgaris (p. vulgaris), 4 EBS, 4 blister beetle, 5 miliaria crystallina, 3 pompholyx, 4 nummular eczema, 2 SJS, 1 TEN, 2 zinc deficiency, and 3 PCT cases. Males outnumber females in age group 0-1 years (14/20) and 1-6 years (31/48), while females were more commonly affected in the age group of 6-14 years (17/32) [Table 1]. Disease incidence: Impetigo [Figure 1] was found to be the most common vesiculobullous disease with the highest incidence of 42%. Among the immunobullous diseases CBDC [Figure 2] was found to be the most common with the incidence of 7% closely followed by DH (6%) [Figure 3]. Pemphigus was rarely reported. Disease specific age incidence: Most of the diseases showed maximum incidence in the age group of 1-6 years except pemphigus, TEN, PCT, which was most common in 6-14 years of age group and EBS which was the only disease to show maximum incidence in the age group of 0-1 years. Disease specific sex incidence: Male predominance was seen in all diseases except Varicella, EBS and PCT where female predominance was seen. Herpes simplex, DH, nummular eczema, SJS, zinc deficiency were equally common in both sexes. Presenting symptoms: Almost all the patients had either skin involvement or both skin and mucous membrane involvement. Exclusive mucous membrane was found to be involved in only one case of SJS. Pain and pruritus were the common symptoms [Table 2]. Morphology of lesions: Varicella, herpes simplex, CBDC and DH presented with tense blisters whereas pemphigus [Figure 4], SJS and TEN presented with flaccid blisters with raw areas and crusting [Table 3]. Pompholyx and bulbous scabies patients had tense blisters on normal looking skin. DH, pemphigus, and TEN lesions healed predominantly with post inflammatory hyper pigmentation.
|Figure 1: Bullous impetigo: Vesicles and bullae filled with turbid fluid, few ruptured leaving crusted erosions|
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|Figure 2: Chronic bullous disease of childhood: Tense vesicles and bullae on normal looking skin with characteristic string of pearls sign|
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|Figure 3: Dermatitis herpetiformis: Grouped pleomorphic lesions with papules, vesicles, erosions and crusting on extensors of upper and lower limbs (mucosal sparing in all cases)|
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|Figure 4: Pemphigus vulgaris: Flaccid bullae with moist erosions, and mucosal involvement|
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| Discussion|| |
As in the present study, several other studies on the pattern of skin diseases in children worldwide also reported a slight male predisposition. ,,
Highest incidence in the age group of 1-6 years (48%) can be attributed to the difference in exposure rates, outdoor activities and lack of awareness in this age group which predominantly includes the school going children.
Further higher opportunity of the male children getting in contact with the infectious agents due to the difference in their pattern of clothing, outdoor activities and contact with other children through schools can be the reason behind male preponderance.
That impetigo is most common in the preschool and school age children, was further supported by other studies. ,
In the present study, Varicella carried the maximum incidence in the age group of 1-6 years. As reported by Meyer et al., 90% of the cases occur in children younger than 10 years of age and fewer than 5% occur in older individuals. 
Blister beetle dermatitis showed wide variation in the sex incidence with 75% male involvement. Similar views are shared by Padhi et al. 
Our view of CBDC being more common in males and having highest incidence in children younger than 6 years of age has been supported by Lear et al.  and Marsden et al.  who reported it as a self-limiting disorder which usually begins before the age of 6 years.
Dermatitis herpetiformis was found equally common in males and females and also showed equal incidence in the age groups of 1-6 and 6-14 years. Stanley et al. reported its maximum onset between 20 and 40 years of age but also mentioned that no age group is immune, including children and also reported its incidence in males twice more common than in females. ,
Only two cases of pemphigus were reported in the present study period one each of p. vulgaris and p. foliaceus, both the cases being males. The cases were reported only in the age group of 6-14 years. The similar data was presented by Bjarnason and Flosadσttir  who described the mean age of onset of childhood pemphigus as 12 years, and also reported male to female ratio of 1:0.96, while it was reported as 1:1.26 in another study by David et al. 
In the present series, infections and infestations were found to be the commonest group of blistering diseases with a total incidence of 57%.
Most common infection was found to be impetigo with 42% incidence, and most common infestation was scabies with incidence of 6%. Brown et al. and Sladden and Johnston, described impetigo as the most common bacterial skin infection and the third most common skin disease overall, after dermatitis and viral warts. , Karthikeyan et al.  also found infections and infestations as the most common dermatoses (54.4%) in their study. Several other authors have also shared the same view. ,,,
Varicella in the present study was found to be the most common viral infection with a total incidence of 7%. 
All these studies reported scabies to be one of the commonest dermatosis in children. This is in contrast to our study where scabies constitutes only 6% of the total cases. This difference is because vesiculobullous presentation of scabies is not common, and all the prior studies done on the pattern of skin diseases in pediatric age group till date have taken cases of common scabies.
Jordon et al. called childhood pemphigus as a rare disease that comprises only a minority of the immunobullous diseases seen in children,  a statement that holds true in the present study which observed only two cases of pemphigus in children.
The diseases such as subcorneal pustular dermatosis, congenital syphilis, incontinentia, and Staphylococcal scalded skin syndrome, often reported in the literature to give rise to vesiculobullous lesions, were not encountered in the present study. This might be due to rarity of the disease.
Stevens-Johnson syndrome and TEN were rarely reported which might be due to the limitation of giving drugs to children by the parents.
All cases of impetigo presented with only skin involvement, with a face being the most commonly affected site. This view is shared by other authors , who reported predominant involvement of face and neck in their study on clinicobacteriological profile of impetigo in children. The proximity to the common carrier sites like nares and throat may be responsible for the increased incidence at these sites. However, some studies  showed extremities as the predominant site of involvement.
Patients with CBDC showed predominant skin involvement, with mucosal involvement in only 29% (2/7) of the patients. Involvement of mucosa in CBDC have already been reported in earlier studies. ,
None of the patients of DH showed mucosal involvement, and this is supported by Lδhteenoja et al.  who reported mucosal involvement to be uncommon in DH. However, Fraser et al.  reported asymptomatic oral lesions. Although no area of skin was spared, extremities were seen to be most commonly involved with extensors showing predominant involvement. Lesions were pleomorphic with tense vesicles, papules, excoriations and postinflammatory hyperpigmentation. Pruritus was complained by all the patients. Lemberg et al.,  Fry and Seah  concluded pruritus being one of the important diagnostic criteria for DH. Further systemic features like toxemia and pyrexia was not a feature which is further supported by Tolman et al. who reported it to be a disease uncommonly associated with toxic features. 
The presentation of p. vulgaris was quite similar to that seen with adults, and the same has been forwarded by Merchant and Weinstein. 
Pemphigus foliaceus presented with crusted erosions in circinate pattern, predominantly involving trunk and extremities. Vesicles although uncommonly seen, were present predominantly around the crusted erosions. This finding is supported by Metry et al.,  who reported crusted plaques and erosions as the most commonly described primary lesions in PF and also described superficial vesiculobullous lesions to be infrequent. Jones et al.  reported circinate/annular lesions to be unique to childhood PF.
Most common lesions in varicella were found to be tiny vesicles, few showing crusting and raw erosions, with post inflammatory hyperpigmentation in few. Bullous lesions in varicella is very rare, and only one case has been reported from India by Sathyanarayana. 
Patients of bullous scabies presented with tense vesicles and bulla similar to that seen with bullous pemphigoid. Diagnosis was mainly based on history and clinical findings. More typical lesions of scabies along with bullous lesions were seen to be present on the typical sites of scabies, that is, web spaces, lower abdomen, genitalia, and in the present series palms and face was also seen to be involved. Patients <10 years of age with tense bullous eruption mimicking bullous pemphigoid, at sites typical for scabies, having had been treated well with permethrin 5% have been reported. ,,
Blister beetle dermatitis presented with exclusive skin involvement. Predilection for face and extremities was shown. This can be explained on the basis of accessibility of beetles for the exposed areas of the skin. Pruritus and burning were the predominant symptoms and kissing lesions were seen in 25% cases, similar to that seen in other studies on beetle dermatitis. ,
| Conclusions|| |
There have been extensive research and rapid developments in the field of pediatric dermatology in the last few decades. Although there are various published studies on pediatric dermatology, but no studies have been attempted describing exclusively, the profile of vesiculobullous diseases in children as a whole under one roof.
The present study concludes that clinical observations remain the key toward the diagnosis and lab investigations can in no case provide any shortcut to the diagnosis. Bullous disorders in childhood are often misdiagnosed and hence causing false incidence reports. Our knowledge in this field still remains in infancy and need to be upgraded in the years to come.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3]