A case of lipoatrophy following quadrivalent human papillomavirus vaccine administration
Authors: Farid Stéphan, Joelle Korkomaz, Gerard Abadjian, Jad Okais, Roland Tomb
Journal: Journal of the American Academy of Dermatology (2014)

To the Editor: Lipoatrophy is a localized loss of subcutaneous adipose tissue without significant inflammation.1Soós N. Shakery K. Mrowietz U. Localized panniculitis and subsequent lipoatrophy with subcutaneous glatiramer acetate (Copaxone) injection for the treatment of multiple sclerosis.Am J Clin Dermatol. 2004; 5: 357-359Crossref PubMed Scopus (33) Google Scholar Acquired forms result from physical trauma (cold, trauma, factitious insults) or from contact with noxious chemicals.2Haas N. Henz B.M. Bunikowski R. Keitzer R. Semicircular lipoatrophy in a child with systemic lupus erythematosus after subcutaneous injections with methotrexate.Pediatr Dermatol. 2002; 19: 432-435Crossref PubMed Scopus (19) Google Scholar It is a common reaction at the level of injection sites and could appear at a distant site months or years after the injection. Several drugs have been implicated, including insulin and insulin analogs in diabetes, glatiramer acetate in multiple sclerosis, corticosteroids, vasopressin, antibiotics, human growth hormone, iron dextran, diphtheria-pertussis-tetanus immunization serum, and antihistamines.1Soós N. Shakery K. Mrowietz U. Localized panniculitis and subsequent lipoatrophy with subcutaneous glatiramer acetate (Copaxone) injection for the treatment of multiple sclerosis.Am J Clin Dermatol. 2004; 5: 357-359Crossref PubMed Scopus (33) Google Scholar We report a case of lipoatrophy that could be associated with injection of prophylactic quadrivalent human papillomavirus vaccine Gardasil. A 27-year-old woman presented to the dermatology clinic with a circular depression on her right arm without any local symptoms or previous inflammation. She had no medical problems and was not taking any medication. She reported a history of 3 intramuscular Gardasil injections on a 0-, 2-, and 6-month-schedule in the same arm, with the last injection given 9 months before the appearance of the lesion. The patient denied any other injection (foreign body or steroids) or trauma to the involved arm. Physical examination revealed a soft, nontender, 8- × 5-cm skin depression. The patient also had a burn scar on the anterior aspect of the arm since childhood (Fig 1). Laboratory studies including complete blood count, serum glucose, lipase, cholesterol, triglycerides, and complement level, as well as renal and hepatic parameters, antinuclear antibody, ds-DNA, and U1RNP were within normal range. Magnetic resonance imaging of the arm showed atrophy of the subcutaneous fat facing the posterolateral fibers of the medial third of the deltoid muscle with adherence of the muscle to the skin. There was no evidence of any expansive process or fat infiltration of the muscle. A biopsy was performed to rule out lupus panniculitis, scleroderma, and cutaneous T-cell lymphoma. Histology with immunofluorescence showed small adipocytes in the hypodermis with lipophages and some lymphocytes surrounded by fibrosis compatible with lipoatrophy. Deep cuts showed macrophagic infiltration within which grayish granulations exist, an image compatible with aluminum granuloma (Fig 2). Each dose of Gardasil contains HPV 6, 11, 16, and 18 with amorphous aluminium hydroxyphosphate sulphate as adjuvant.3Crum C. Jones C. Kirkpatrick P. Fresh from the pipeline: quadrivalent human papillomavirus recombinant vaccine.Nat Rev Drug Discovery. 2006; 5: 629-630Crossref PubMed Scopus (10) Google Scholar The latter is used in multiple vaccines such as tetanus toxoid, hepatitis B, and diphtheria-pertussis-tetanus and in allergen immunotherapy with the aim of prolonging and augmenting the immune response to the antigen.4Chong H. Brady K. Metze D. Calonje E. Persistent nodules at injection sites (aluminium granuloma) – clinicopathological study of 14 cases with a diverse range of histological reaction patterns.Histopathology. 2006; 48: 182-188Crossref PubMed Scopus (75) Google Scholar It is known to cause aluminium granuloma with a diverse range of histologic reaction patterns.4Chong H. Brady K. Metze D. Calonje E. Persistent nodules at injection sites (aluminium granuloma) – clinicopathological study of 14 cases with a diverse range of histological reaction patterns.Histopathology. 2006; 48: 182-188Crossref PubMed Scopus (75) Google Scholar Atrophy and fibrosis of subcutaneous fat have been described by Chong and colleagues.4Chong H. Brady K. Metze D. Calonje E. Persistent nodules at injection sites (aluminium granuloma) – clinicopathological study of 14 cases with a diverse range of histological reaction patterns.Histopathology. 2006; 48: 182-188Crossref PubMed Scopus (75) Google Scholar The histologic features in our case are more indicative of a foreign body reaction to aluminium hydroxide than of an allergic reaction.5Vogelbruch M. Nuss B. Körner M. Kapp A. Kiehl P. Bohm W. Aluminium-induced granulomas after inaccurate intradermal hyposensitization injections of aluminium-adsorbed depot preparations.Allergy. 2000; 55: 883-887PubMed Google Scholar To our knowledge, lipoatrophy following injection of the quadrivalent human papillomavirus vaccine Gardasil has not been described before. We did not find in this case any other cause that could be related to lipoatrophy unless trauma of the injection itself is an etiology.2Haas N. Henz B.M. Bunikowski R. Keitzer R. Semicircular lipoatrophy in a child with systemic lupus erythematosus after subcutaneous injections with methotrexate.Pediatr Dermatol. 2002; 19: 432-435Crossref PubMed Scopus (19) Google Scholar We estimate that the injection was subcutaneous instead of intramuscular and that the aluminium granulations found in the macrophages correspond to the adjuvant found in the vaccine.