Plaque psoriasis following Kawasaki disease and varicella

Abstract

We describe the case of a 15-month-old boy with Kawasaki disease who developed varicella 7 days after the beginning of the disease and diffuse plaque psoriasis after 43 days. Associations between Kawasaki disease and psoriasis, between Kawasaki disease and varicella and between varicella and psoriasis have all been reported in the literature. The triple association of Kawasaki disease, varicella and psoriasis is very rare. Neither the double nor the triple associations are well known among a diverse group of practitioners.

Background

Kawasaki disease (KD) is an acute vasculitis of unknown aetiology that mainly affects children younger than 5 years of age. The diagnosis is based on clinical criteria: fever persisting for 5 days or more, and at least four of five principal clinical features: oral mucous membrane changes, polymorphous rash, bilateral bulbar conjunctival injection, peripheral extremity changes and cervical lymphadenopathy.¹ The disease progresses in three stages: the acute febrile stage lasting about 10–12 days, the subacute stage lasting 2 weeks which is associated with the development of coronary aneurysms in 20%–25% of the untreated children and the convalescent stage lasting about 6 weeks until normalisation of the inflammatory parameters.

The aetiology of KD is not known. It is believed that an infectious agent induces an abnormal immune response in genetically predisposed individuals.² Infection with varicella zoster virus (VZV) has been associated with KD in a few reports.^3–9

The occurrence of psoriasis in the acute, subacute or convalescent phase of KD has been described in several reports.^10–22 Imbalance between upregulated T-helper 17 (Th17) cells and downregulated regulatory T (Treg) cells, leading to increased expression of interleukin (IL)-17, plays a role in the pathogenesis of KD.²³ Th17 cells and IL-17 are involved in the pathogenesis of psoriasis as well.²⁴

Varicella has also been described as a possible inducer of psoriasis. Immunological mechanisms as well as the Koebner phenomenon appear to be involved.^{25 26}

The triple association of KD, varicella and psoriasis is rare, we have not found any citation in PubMed.

Case presentation

A 15-month-old boy was admitted with high fever and vomiting since 3 days. The temperature was 39.1° C. At physical examination, he appeared ill without a clear focus for the fever. The abdomen was tender. Blood examination revealed 9.2×10⁹/L white cell count (WBC), with 31% band forms, 29% segmented neutrophils and 29% lymphocytes; the haemoglobin concentration was 108 g/L, platelet count was 405×10⁹/L; C reactive protein was 191 mg/L. Urine examination showed 459 WBC/µL (culture proved negative later, as well as haemoculture). A chest radiograph and abdominal ultrasonography were normal. Septicaemia was suspected and treatment with cefotaxime was started. Despite therapy the fever persisted and 2 days after hospitalisation (on the fifth day of fever) he developed red and dry fissured lips, hyperaemic oral mucosa, a strawberry tongue, skin rash, bilateral conjunctivitis, cervical lymphadenitis and oedematous hands and feet. KD was diagnosed. Treatment with intravenous immunoglobulins 2 g/kg and acetylsalicylic acid 80 mg/kg/day was initiated. The fever disappeared on the following day. Echocardiography revealed no coronary lesions and the dose of acetylsalicylic acid was reduced to 5 mg/kg/day. On the seventh day, he developed varicella. He was discharged on day 9.

Ten days later, on day 19, he developed fever up to 39°C again. At physical examination, he had crackled lips and peeling of the skin on fingertips and toes. All varicella lesions were dry. Blood examination revealed 15.6×10⁹/L WBC with a normal differential and 600×10⁹/L platelets; the C reactive protein was 96,1 mg/L. Urine examination demonstrated 52 WBC/µL. A second dose of intravenous immunoglobulins was administered. Echocardiography remained normal and the fever disappeared after 1 day. He was discharged, but 1 day later, Staphylococcus aureus was cultured from the urine. Since he was generally well and demonstrated no signs of urinary tract infection, treatment with antibiotics was not initiated and the organism was considered as a contaminant.

Three weeks later, on day 43, clinical examination during follow-up visit revealed multiple nummular, erythematous and desquamating skin lesions at the site of healed varicella lesions. Plaques were seen on the trunk and the proximal extremities. Perioral lesions with hyperaemic mucosa and crackles around the lips were present as well. The dermatologist classified these lesions as diffuse plaque psoriasis (figure 1). Treatment with topical mometasone furoate 1 mg/g supported resolution of the lesions within 3 weeks.

Figure 1.

Diffuse plaque psoriasis lesions.

Outcome and follow-up

There was no recurrence of lesions at follow-up 1 year later. Familial history revealed that the paternal grandmother suffered from psoriasis.

Discussion

Autoimmune phenomena can be triggered by environmental factors in genetically susceptible individuals. Among environmental factors Infections are an important trigger.²⁷ Therefore, coincidental or sequential presentation of infections and autoimmune problems is not rare.

Many bacterial and viral agents have been associated with KD, although their role is not entirely clarified.¹ Among these agents, VZV has been associated with KD. Varicella preceding KD was reported in four articles and during the acute stage in three articles.^3–9 Thus, infection with VZV might be a trigger for KD. VZV replicates in the body during its incubation period (11–20 days) and viraemia can be detected as early as 10 days before the occurrence of rash.^{28 29} Our patient developed varicella skin lesions during the acute phase of KD, 7 days after the onset of fever. Thus, we assume that VZV triggered KD in our patient.

The association of KD with psoriasis has been reported in at least 32 children.^10–22 A synopsis of these cases is shown in table 1. Psoriasis associated with KD is mostly plaque psoriasis and resolves without recurrences.

Table 1.

Cases of Kawasaki-induced psoriasis described in the English literature

Author, year	Numbers of patients	KD phase during which psoriasis arose	Type of psoriasis	Localisation	Time for the psoriatic lesions to disappear	Familial predisposition for psoriasis
Han et al,10 2000	1	Subacute phase	Guttate psoriasis	Face, trunk, extremities	Gradually disappearing	Not described
Eberhard et al,11 2000	10	Subacute phase:five patients Convalescent phase:five patients	Pustular Psoriasis: three patients Plaque psoriasis: seven patients	Trunk, extremities Trunk, knees, elbows	Rapidly resolving with no recurrence	Two patients
Garty et al,12 2001	1	Subacute phase	Guttate psoriasis	Trunk, extremities	1 year after disappearance of KD	Not described
Boralevi et al,13 2003	1	Convalescent	Pustular and guttate psoriasis	Trunk, extremities	2 months	Not described
Zvulunov et al,14 2003	1	Acute phase Convalescent phase	Pustular psoriasis Plaque psoriasis	Sole of a foot Cheeks, extensor side extremities	Gradual, spontaneous disappearing	Not described
Menni et al,15 2006	1	Acute phase	Plaque psoriasis	Trunk	2 months	Not described
Mizuno et al,16 2006	1	Convalescent phase	Plaque psoriasis (psoriasis vulgaris) Pustular lesions	Cheeks, extensor region left upper arm (BCG vaccine) Palms and soles	Gradual disappearing	Not described
Yoon et al,17 2007	1	Subacute phase	Plaque psoriasis	Extremities, trunk	1 month	Not described
Liao and Lee,18 2009	1	Acute phase	Psoriasiform papules and plaques	Face, extremities	1 month	Not described
Ergin et al,19 2009	1	Subacute phase	Plaque psoriasis	Cheeks, trunk, extremities	3 weeks	Mother
Kishimoto et al,20 2010	1	Acute phase – after intake of infliximab	Psoriasiform papules and plaques	Extensor surface extremities	Few weeks	Not described
Haddock et al,21 2016	11	Acute phase: two patients Subacute phase: three patients Convalescent phase: six patients	Plaque psoriasis: nine patients Guttate psoriasis: one patient Psoriatic nail pitting: one patient	Diaper area, trunk, extensor extremities, face	1.6 to 17.9 months	One patient
Geller and Kellen,22 2017	1	Subacute phase	Plaque psoriasis	Face, arms, legs	3 weeks, no recurrence	Not described

KD, Kawasaki disease.

Psoriasis developing after varicella infection has also been reported in the literature.25 26 30–32 Plaque or guttate psoriasis lesions appear after 2 weeks to 3 months on skin areas that were affected by varicella. This is probably related to the Koebner phenomenon (the appearance of psoriatic lesions on the skin of psoriatic patients as a consequence of local trauma). Family history of psoriasis in an affected patient and resolution without recurrence has been described in one article.³⁰

Proinflammatory cytokines, among others interferon γ, tumour necrosis factor alpha and IL-6, are produced during the acute phase of KD or varicella.^{14 33} Activation of myeloid dendritic cells by these cytokines leads to activation of Th17 cells and expression of IL-17/IL-22. IL-17 appears to play an important role in KD, but is also known to be involved in the pathogenesis of psoriasis by activating keratinocytes to produce psoriasis associated molecules. On resolution of KD, the amount of cytokines in the inflammatory environment diminishes, downregulating the T-cell response and therefore leading to resolution of the psoriatic skin lesions.^{11 15} Hence, similarities in immunological pathways may induce the development of psoriatic lesions in persons with a psoriatic constitution.^{24 34 35} This is an example of how immunological processes can lead to coincidental associations of infection and autoimmune pathology in genetically predisposed persons.

Our patient developed plaque psoriasis at the site of healed varicella lesions suggesting a Koebner phenomenon induced by local skin damage caused by the chickenpox. As the family history revealed psoriasis in his paternal grandmother, we hypothesise the presence of a genetic predisposition promoting induction of psoriatic lesions by KD or varicella or both. It is reported that psoriatic lesions after KD tend to disappear gradually. In our patient, the lesions disappeared after 3 weeks, without recurrence at follow-up after 1 year. It is not clear if the development of psoriatic lesions after KD and varicella entails the development of psoriasis later in life.

As varicella has been associated with Reye syndrome, the use and dosage of acetylsalicylic acid in our case can be a matter of discussion. Our patient presented in 2013 and at that time high doses of acetylsalicylic acid were commonly used in the acute phase of KD. When treatment was initiated, no varicella lesions were present. When they appeared, the dosage was already reduced to low dose. Although a low dose for antiplatelet effect has not been associated with Reye syndrome, acetylsalicylic acid could have been replaced by another antiplatelet agent such as thienopyridine.¹

Conclusion

Triggering of autoimmune phenomena by infection and similarities in immunopathogenesis can explain the triple association of varicella, KD and psoriasis in our patient. This triple association is rare. Double associations between KD and psoriasis, varicella and psoriasis, and KD and varicella have been described but are not well known. We consider this case report as an opportunity to highlight these aspects of KD.

Learning points.

• Associations between Kawasaki disease (KD) and psoriasis, varicella and psoriasis, and KD and varicella have been reported in the literature, but the triple association varicella, KD and psoriasis is rare.

• Triggering of autoimmune phenomena by infection in genetically predisposed individuals and similarities in their immunopathogenesis can explain coincidental or sequential associations between these pathologies.

• Psoriatic lesions after KD disappear gradually. Whether the development of psoriatic lesions after KD and varicella entails the development of psoriasis later in life in not known.