Bullous varicella in a preschool-aged patient

INTRODUCTION

Varicella (chickenpox) is a highly contagious febrile rash illness caused by primary infection with Varicella zoster virus (VZV/HHV-3), which is one of the eight human herpes viruses, transmitted by respiratory contact with aerosolised respiratory secretions and blister secretions or by direct contact with them [1].
The world annual incidence of varicella is estimated at 80–90 million cases. Prior to the introduction of the varicella vaccine in 1995, there were 4 million cases, over 11 thousand hospitalisations, and 100–150 deaths annually in the United States, the majority of which occurred in children. Implementation of the one-dose routine varicella vaccination program in 1996 resulted in a 90% decline in varicella incidence, and adding a second dose in 2006 resulted in an additional 85% decline in the disease [2]. It is most commonly seen in children under the age of 10 years in countries where live attenuated varicella vaccine is not routinely administered [3]. Varicella vaccine is not included to the immunisation calendar of Ukraine as a planned obvious vaccination of healthy children, although 120–150 thousand cases of varicella are registered annually in the country [4, 5].

CASE REPORT

The typical course of varicella in immunocompetent unvaccinated children is generally mild and uncomplicated. We present a case of an atypical bullous varicella from our practice.
A boy of 5 years 10 months entered the infectious department on the fourth day of his disease. On admission he complained of big blisters, “honey” crusts on his perioral region, left ear, neck, trunk, and legs, and vesicles all over the body and on the scalp, body temperature 38.5°С, malaise, and poor appetite.
Present history: the disease began four days earlier from maculopapular rash on the scalp and trunk, and body temperature was 38.5°С. The next day, a new rash appeared on the head, trunk, and extremities, previous elements changed to vesicles, and body temperature grew up to 39.2°С. The boy was treated symptomatically (antipyretics, local antiseptics). A few erythematous macules 3–4 cm in diameter appeared on his shins and the left ear on the third day and changed to bullae in a few hours; body temperature was febrile. Massive similar erythema appeared on his thighs, neck, trunk, and near the mouth during the subsequent night, although he was hospitalised on the fourth day of the disease.
Past history was unremarkable. The boy was not immunised with varicella vaccine. He had contacted an ill sister who started typical varicella 16 days before him. On admission the patient’s general condition was moderately grave because of toxic and skin syndromes. He was conscious, lying on his back, with partly flexed hips and knees. Vital signs: HR 126, RR 22 per minute, SpO2 97%. Vesicular rash 0.2–0.3 cm with cloudy content was seen all over the body, predominantly on legs. Bullous flat, sometimes confluent, partly eroded or centrally crusted rash 3–5 cm was present predominantly on his thigs, shins, trunk, neck, and left ear; large “honey” crusts periorally, on the forehead; and small crusts on the scalp and face (Fig. 1).
Visible mucosa was pinkish with two erosions on the soft palate. Anterior and posterior cervical, suboccipital, submandibular lymphatic nodes up to 0.8 cm in diameter were painless, elastic, and movable on palpation. Meningeal symptoms were negative. Breathing was vesicular, and heart tones were loud and rhythmic. Abdomen was soft and painless, with mild hepatosplenomegaly (+2 and +1 cm correspondingly) on palpation. Urination was regular, but constipation was present for three days. In laboratory tests, CBC showed monocytosis on admission and mild lymphocytosis at discharge (Table 1). Blood biochemical test was within the reference range (Table 2).
Immune-enzyme test done on the fourth day of exanthema showed specific varicella-zoster (VZV) antibodies: IgM – 3.22 IU (positive) and IgG – 0.48 IU (negative). Bacterial culture of the bulla’s exudate on admission was negative. Basic immunological tests were not performed. Hence, atypical bullous varicella was diagnosed.
The patient was treated according to national Ukrainian guidelines [6]. Aetiological therapy included oral acyclovir 400 mg (20 mg/kg) 4 t.d. for seven days; pathogenetic therapy with polyvalent intravenous immunoglobulin (IVIG) 100 ml of 10% solution (0.5 g/kg) for three days, and intravenous detoxication (200 ml of 0.9% NaCl solution and 200 ml of 5% glucose solution twice a day) for three days; symptomatic therapy was given with antipyretics and antihistamines to decrease itching, as well as local antiseptics. Cefazolin in average doses was given for seven days intravenously empirically to prevent bacterial contamination of erosions, in spite of negative bacterial culture obtained later.
In dynamics, the patient’s body temperature normalised until the next evening, and there were no new lesions; bullous lesions increased in diameter up to 4–6 cm on the fifth day of illness (second day in the hospital) and started healing without new erosions (Fig. 2A and 2B). Oral erosions healed within four days and bullae epithelised completely with slight pigmentation in eight days of admission (12th day of illness) (Fig. 2C and 2D). Therefore, the patient was successfully discharged.
In follow-up, the boy was examined one year later: he was generally healthy, the skin in the location of previous lesions had normal colour and structure without pigmentation or scarring, and no late complications developed for this period.

DISCUSSION

The typical course of varicella in immunocompetent unvaccinated children is generally mild with pruritic rash that progress within 24–48 hours from macules to papules and vesicles on an erythematous base with clear fluid before crusting. The rash primarily appears on the scalp, crops 2–4 times in 4–6 days with trunk and extremities involvement, but has centripetal distribution. Lesions then crust over and fall off in the next 1–2 weeks. Lesions also can occur on mucous membranes of the oropharynx, respiratory tract, genitals, and conjunctiva. Lesions seen on the third to fifth day of the disease are usually 1–4 mm in diameter and pleomorphic. 200–500 are usually seen in typical moderate varicella. The rash is accompanied with malaise and moderate fever for 2–3 days. The illness usually lasts about a week [2].
Varicella has atypical course in vaccinated persons known as “breakthrough varicella” due to infection with wild type VZV, which occurs more than 42 days after varicella vaccination. It is characterised with less than 50 lesions of maculo-papular character with no or few vesicles, low-grade fever, and short duration. It is less contagious than primary varicella. However, the clinical features typical for varicella can develop in 25–30% of vaccinated persons as in unvaccinated [1, 3]. Congenital varicella and neonatal varicella also belong to atypical clinical forms [2, 7].
The diagnosis of VZV infection is usually made clinically by the appearance of the typical skin rash. In confusing or unusual cases, the diagnosis may be made by identifying VZV DNA in skin lesions by PCR or specific IgM measurement [1].
Varicella in the healthy immunocompetent host is usually a mild self-limited disease, but complications can occur. Groups at increased risk for severe atypical disease course and complications include neonates and infants, adolescents, adults, and immunocompromised patients. Complications such as bacterial skin superinfections, pneumonia, bronchitis, laryngotracheitis, and gastrointestinal tract disorders are the most characteristic in children under two years of age. Cerebellar ataxia, encephalitis, aseptic meningitis, transverse myelitis, and Guillain-Barre syndrome are the main viral CNS complications, they are more frequent in children 3–6 years of age [8, 9]. Peripheral facial palsy, described by Hanalioğlu et al. [10], is an extremely rare neurologic complication of varicella. One more extremely rare neurologic complication (Vernet syndrome, a unilateral palsy of glossopharyngeal, vagus, and accessory nerves) was presented by Ferreira et al. [11]. Other viral complications include glomerulonephritis, myocarditis, arthritis, orchitis, uveitis, iritis, acute retinal necrosis, mild hepatitis, and pancreatitis. Reye syndrome as an unusual complication of varicella occurs almost exclusively in children who take aspirin during the acute illness. Haematological disorders include mild neutropaenia and thrombocytopaenia, rare purpura fulminans, disseminated intravascular coagulation, and Henoch-Schönlein purpura, which could be clinically presented as “varicella haemorrhagica” [2, 12–15]. Acute liver failure (ALF) and hemophagocytic lymphohistiocytosis (HLH) are extremely rare complications induced by VZV infection [16].
Secondary bacterial infection of skin lesions, usually due to Staphylococcus aureus or Streptococcus pyogenes, and secondary bacterial pneumonia dominate among other bacterial complications [2, 7]. Staphylococcal or streptococcal toxic shock syndrome, osteomyelitis, necrotising fasciitis (previously known as “varicella gangrenosa”, caused by exotoxin of group A β-haemolytic streptococci, which lead to an extensive local tissue destruction) belong to the group of more serious bacterial complications [13, 17, 18]. Casuistical varicella complication by calvaria osteomyelitis was described by Sommer et al. [19].
Bullous chickenpox, also known as varicella bullosa, is a rarely reported variant of chickenpox (occurring in 0.5% of cases) that can affect both children and adults. It can occur both in previously healthy persons and in immunocompromised ones [20, 21].
In the first case, varicella bullosa resembles ordinary primary varicella but is complicated by the formation of giant flat bullae 2–3 cm or more in diameter with cloudy serous, seropurulent, or serosanguinous content and the formation of large erosions, when blisters ruined. Varicella bullosa has a mainly benign course with slightly longer epidermis healing and slight pigmentation – up to two weeks usually. Despite bullous skin lesions, mucosa changes may be absent or small and not numerous. General symptoms are usually mild to moderate [22–25]. Such a course of the disease, with moderate general symptoms, was seen also in our patient. Initially, it had a typical beginning, as in varicella in unvaccinated immunocompetent persons; bullous elements appeared on the third day of the disease and progressed without specific treatment. In spite of massive confluent skin lesions there were few small lesions on oral mucosa only. Due to the combination of specific antiviral medicine, adequate doses of polyvalent intravenous immunoglobulin, and systemic and local antibacterial treatment, the patient’s disease resolved completely through healing of all bullous lesions with slight pigmentation up to the 12th day of his illness.
If varicella bullosa occurs in an immunocompromised person, it usually has a severe relapsed course with large elements, poor prolonged healing for more than three weeks, and secondary complications [26, 27].
Despite the fact that toxigenic Staphylococcus aureus is considered to play the main role in the aetiology of varicella bullosa [26, 27], in some patients, vesicles cultures were negative [24, 25]. Bacterial culture taken from the patient’s bullae before initiation of antibacterial therapy was also negative. The pathogenesis of bullae remains unclear; it is either a distinct manifestation of VZV or the result of coinfection with exfoliative toxin-producing Staphylococcus species. Bullae may represent coalescence of multiple vesicles or result from superimposed bullous impetigo/staphylococcal scalded skin syndrome [28]. The histopathology is distinct from bullous impetigo and comprises intraepidermal bullae with multinucleated keratinocytes (giant cells) and intranuclear inclusions demonstrated by Tzank smear, which is characteristic for varicella [24, 26]. Modern techniques including polymerase chain reaction strongly support varicella zoster virus involvement in the development of bullae [29]. The VZV aetiology of the disease in our patient was proven immunologically by measuring specific IgM antibodies without histopathological examination.
Routine treatment of varicella in healthy children is not uniformly recommended, although an oral form of the acyclovir is available for children 2–12 years of age in typical uncomplicated severe cases, and for adolescents in moderate to severe cases. For the best outcome, antivirals should be given as soon as possible to immunocompromised individuals and to anyone who seems to be developing severe varicella [1]. However, treatment of varicella bullosa includes average recommended doses of acyclovir for 1–2 weeks depending disease severity and antistaphylococcal antibiotics for 10–14 days together with adequate supportive care. Adjunctive therapy with intravenous immunoglobulin may also be beneficial in patients with streptococcal cutaneous complications. The prognosis of this form of chickenpox is usually excellent [25]. In the presented case the patient was treated successfully with complete recovery according the national Ukrainian guidelines with an adequate dose of acyclovir, its combination with polyvalent intravenous immunoglobulin, and antibacterial and symptomatic therapy, which corresponds to modern European guidelines [30, 31].

CONCLUSIONS

Bullous varicella is a rare atypical form of varicella in immunocompetent children, which has some clinical and morphological peculiarities. Adequate, timely treatment of bullous varicella in immunocompetent children, according modern guidelines, leads to complete recovery in a short period of time. Vaccination with a live attenuated varicella vaccine is the single effective method to prevent severely complicated disease, and it is recommended for inclusion in the immunisation calendar of Ukraine for obvious vaccination of healthy children from 12 months of age.

DISCLOSURE

The authors declare no conflict of interest.

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