Review
Gianotti-Crosti syndrome

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History

In July 1953 Ferdinando Gianotti examined a child with a monomorphous erythematous papular rash confined to the extensor surfaces of the arms and legs. The boy had generalized lymphadenopathy but was otherwise well. Gianotti was a resident at this time. He was unable to fit this patient into any established diagnosis and suspected he was on to something new. During the next months, he saw a number of patients with the identical skin findings. A particularly instructive case occurred when a

Epidemiology

GCS has a worldwide distribution but is undoubtedly underdiagnosed,18 making it impossible to estimate the incidence. Almost all patients are between 3 months and 15 years of age, with a peak between 1 and 6 years of age.19, 20 According to Frieden and Penneys,20 more than 90% of patients are younger than 4 years. On the other hand, there are numerous case reports of GCS in adults,21, 22, 23, 24, 25, 26, 27, 28, 29 where exclusively women (average age 29.5, range 17-45 years) are affected (

Origin

The pathogenesis of GCS is much less clear than suggested a quarter-century ago when the connection with HBV was established. Viral infections are still the key factor and many have postulated an infectious-allergic pathway.32, 33

The major HBV subtypes are adr, ayr, adw, and ayw; the last two are most common in Europe,34 but the ayw subtype from southern Europe is most often connected with GCS.9, 11 In contrast, in southeast Asia the responsible subtypes are usually adr and adw.11, 35

Today, HBV

Pathogenesis

The pathogenesis of GCS is still unclear, although a number of hypotheses have been proposed. Baldari et al41 consider a viral infection the most important factor and postulate that perhaps a second necessary event is some other form of immunostimulation or immunomodulation. They suggest that this could explain why children with an impaired immune system, such as those with atopic dermatitis,31 are more often affected. Colombo et al9 suggested that either circulating viruses or immune complexes

Clinical features

The disease usually starts abruptly with cutaneous lesions. Sometimes there may be a prodrome with pharyngitis, upper-airway infection, or diarrhea. The cutaneous signs and symptoms seem to depend more on the individual characteristics of the patient than on the causative virus.15 The classic finding is multiple, monomorphous pink to red-brown papules or papulovesicles, which may be slightly pruritic and can become confluent (Fig 2). The individual lesions are 1 to 5 mm in diameter and rarely

Laboratory

The peripheral blood may show modest lymphocytosis or lymphopenia. Occasionally the number of monocytes is increased, probably in patients with EBV.19 If the liver enzymes are elevated, the usual cause is EBV or CMV. Today hepatitis is only rarely associated with CGS, even in developing lands. If hepatitis is suggested, then anti-hepatitis A virus-IgM and -IgG, HBsAg, and anti-HCV-IgG should be sought. Liver biopsy is not indicated but, not surprisingly, shows acute hepatitis with periportal

Histology

The histologic picture of GCS may be dramatic but is not diagnostic. Both vesicular (Fig 7) and nonvesicular (Fig 8) patterns can be seen. The vesicular variant shows striking epidermal changes with mild acanthosis accompanied by diffuse spongiosis and vesicles. The dominant cells in the vesicles are Langerhans cells. Occasionally exocytosis of lymphocytes can be marked, mimicking Pautrier's microabscesses of mycosis fungoides.77 The papillary dermis features an intense lymphocytic perivascular

Clinical differential diagnosis

The clinical picture is usually so distinctive that the diagnosis of GCS is a diagnosis made at first glance. There are a number of differential diagnostic considerations that usually play a greater role in atypical, very early, or resolving cases (Table V). Some of the more important possibilities are considered in more detail.

  • Lichen planus is characterized by intense pruritus, preferential involvement of the volar surface of the wrist, pale violet color, and frequently mucosal involvement. In

Histopathologic differential diagnosis

The histologic picture of GCS is not specific. If the lesions are vesicular, differential diagnostic considerations include allergic contact dermatitis, drug reaction, and arthropod assault. Other lesions resemble pityriasis rosea with focal parakeratosis and spongiosis. When the infiltrates are superficial and deep, erythema annulare centrifugum may be suggested.77, 79

Therapy

Because CGS is both self-limited and associated with few symptoms, in most cases no treatment is required. The lesions blanch and resolve more rapidly with midpotency topical corticosteroids applied once daily for 7 to 14 days but this effect has never been established in a controlled setting. Although worsening of findings with topical corticosteroids has been described,82 it must be very rare and does not pose a contraindication. Systemic corticosteroid pulse therapy has been recommended for

Course and prognosis

The course is benign but often long, at least in the eyes of the patient or parents. The lesions heal without scarring over 10 to 60 days; both extremely rapid (5 days) and very long (12 months) courses have been described.75, 83 Rarely postinflammatory hypopigmentation or hyperpigmentation may evolve.84 Recurrences are possible but rare.85

The lymphadenopathy may persist for several months.11, 68 Similarly, hepatosplenomegaly takes longer to resolve than the cutaneous lesions. The rare cases

Conclusion

GCS is a common well-established clinical entity. Since its first description 50 years ago, the role of viruses and, to a lesser extent, bacteria as triggering agents has been well established. There has been a striking shift from HBV to EBV as the most common cause. How the infectious agents cause the classic cutaneous pattern remains a mystery. Other puzzles are why only a small number of individuals infected with EBV develop GCS and why their clinical features vary so greatly.

The diagnosis

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