ARTICLE
Specific hyposensitization by aluminium-adsorbed vaccines is standard
practice in treatment of IgE-mediated allergies. Mild local cutaneous
reactions occur frequently at the site of injection, but persistent lesions
are less common [1].
We describe two cases with an unusual persistent nodular reaction at
the site of previous immunizations.
Case report
Case 1: A 19-year-old woman presented with multiple itchy
nodules on the outer aspects of the upper part of the arms of eight months
duration. They were located at the site of previous vaccine injections.
Physical examination revealed several nodules ranging from a few millimetres
to 1 cm in diameter, some of them with hyperpigmented overlying skin (Fig.
1). She had been receiving hyposensitization vaccines to treat
recurrent extrinsic asthma and rhinitis for the last four years.
A skin biopsy was performed. Histopathological examination of the specimen
showed a normal epidermis and upper dermis. Multifocal unencapsulated
granulomatous infiltrates were seen in the deep dermis and subcutaneous
tissue disrupting the normal architecture of the latter (Fig.
2A). The infiltrate was predominantly composed of histiocytic
cells, with foreign body giant cells (Fig.
2B). Fibroblasts, fibrosis and perivascular lymphocytes and plasma
cells, with a few eosinophils were also present. A granular basophilic
material was observed within the cytoplasm of some histiocytes. Patch
test with 2% aluminium chloride in petrolatum as well as the Spanish standard
patch test battery (which includes nickel sulfate and potassium dichromate)
were negative. The patient was treated with potent topical corticosteroids
and oral antihistamines achieving some relief, but the nodules still persisted
2 years later.
Case 2: A 37-year-old woman presented with a five-year
history of multiple itchy nodules on the outer aspects of the upper part
of the arms at the site of previous vaccine injections. She had been receiving
hyposensitization vaccines to treat recurrent extrinsic asthma and rhinitis
for 10 years since she was fifteen.
Physical examination and histopathological findings of a biopsy of one
of the nodules were completely identical to those of case 1. Patch test
with 2% aluminium chloride in petrolatum, and the Spanish standard patch
test battery were negative. Symptomatic relief was obtained with topical
corticosteroids and oral antihistamines. The nodules persisted after a
follow-up period of three years.
Energy-dispersive X-ray
(EDX) microanalysis
The stippled macrophages from both biopsy specimens were studied by
EDX microanalysis as previously described [2]. A distinct emission peak
corresponding to aluminium was demonstrated and computerised analysis
located the aluminium inside the macrophage cytoplasms (Fig.
3).
Discussion
The development of palpable nodules after the acute local reaction has
subsided is a known side effect of aluminium containing antigen solutions
in about one third of the patients [3]. The nodules are usually transient
in nature and persist for only a few weeks [1]. Very uncommonly these
lesions persist much longer or develop later. To explain the appearance
of persistent subcutaneous nodules, two nonexclusive mechanisms have been
postulated based on histopathological features and patch tests: a) a non
allergic direct toxic effect (foreign body reaction) of aluminium [4];
and b) a delayed hypersensitive reaction to aluminium [1, 5-7]. The foreign
body reaction is histologically characterized by large histiocytic cells
with a granular grey-purple cytoplasm (corresponding to intracellular
aluminium as has been demonstrated through different procedures [1, 8-10],
a mild to moderate inflammatory reaction with neutrophils, lymphocytes,
and eosinophils. In early lesions, it is also possible to find large amounts
of extracellular basophilic material [8]. In some cases, there is a superimposed
unifocal or multifocal unencapsulated granulomatous reaction with an infiltrate
composed of nodular aggregations of lymphocytes with lymphoid follicles,
large histiocytic cells, abundant eosinophils, and some plasma cells [8].
The latter pattern suggests a delayed hypersensitivity granulomatous type
reaction to aluminium although patch test to aluminium compounds is not
consistently positive [8, 11, 12]. In our two cases, the finding of aluminium
particles in the macrophages supports the hypothesis that it was involved
in the pathogenesis, most probably through a foreign body type of reaction
because of the histological pattern and the negative reaction in the patch
test.
Treatment other than surgical excision is symptomatic
although some improvement can be achieved with oral antihistamines, corticosteroids,
and/or capsaicin cream [8]. The use of aluminium-free vaccines is recommended
since some patients can complain of recurrent episodes of local itching
and pain, usually related to the administration of successive vaccines
or after contact with aluminium-containing objects [1, 3, 5, 7, 11]. Since
the persistent antigenic stimulation in areas with a chronic immune response
could potentially originate a lymphoid malignancy, periodic follow-up
has also been recommended [8].
Persistent nodules during hyposensitization with aluminium containing
allergens may indicate the development of aluminium hypersensitivity and
if this is confirmed hyposensitization should be performed with aluminium-free
vaccines.
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