DR [page 4] [Dermatology Reports 2010; 2:e2] Cutaneous papules in a patient with acquired immunodeficien- cy syndrome Pascale Quatresooz, Claudine Piérard- Franchimont, Philippe Paquet, Gérald E. Piérard Department of Dermatopathology, University Hospital of Liège, Liège, Belgium Abstract During the past decade or so, the incidence of syphilis has increased in most parts of the world. In some urban regions, a coinfection with human immunodeficiency virus is dis- closed in nearly 50% of the cases. Owing to the polymorphism of the lesions, the clinical diag- nosis may be puzzling. The homing patterns and migration paths of Treponema pallidum in the skin during early syphilis represent the preliminary steps preceding dissemination to other organs. Immunohistochemistry directed to T. pallidum is a convenient means for reach- ing the diagnosis and for exploring the dissem- ination process. The present case illustrates the dermal clustering and the vascular spread of T. pallidum in a woman with acquired immu no deficiency syndrome. Introduction A number of skin disorders have been described in patients with acquired immunode- ficiency syndrome (AIDS). Among them, sec- ondary infections are common, but their inci- dence has decreased considerably following the introduction of combined therapies targeted to the human immunodeficiency virus (HIV). Some clinical presentations may be puzzling, particularly in secondary syphilis exhibiting lesions showing a marked tendency to polymor- phism. The histopathological examination often proves to bring about the diagnosis. Design and Methods A 29-year-old woman with a three-year his- tory of AIDS presented with polymorphic papules on the face and abdomen. The lesions reaching 0.5-1.5 cm in diameter had been pres- ent for about two months. They were diag- nosed tentatively as pityriasis rosea, pityriasis lichenoides, and secondary syphilis. The skin lesions were asymptomatic but the patient complained of discrete malaise, stiff neck, myalgia headache, and mild fever. A biopsy specimen was taken from a papule on the abdomen. A series of 5-µm thick sections were cut from the formalin-fixed paraffin-embedded biopsy. An immunohistochemical assessment was performed using a rabbit polyclonal anti- body directed to Treponema pallidum (1:200 Biocare Medical, Walnut Creek, CA, USA). This antibody is highly sensitive for detecting spiro- chetes in human tissues. The avidin-biotin peroxidase method was performed as previ- ously described.1,2 A one-hour incubation time was used with the T. pallidum antibody. The EnVision (Dakopatts, Glostrup, Denmark) polymer-based revelation system and Fast red (Dakopatts) staining were used. Negative immunohistochemical controls were per- formed by omitting or substituting the primary and the secondary antibodies in the laboratory procedure. Results The dermoepidermal junction contained a band-like infiltrate composed mostly of lym- phocytes, histiocytes, and plasma cells. A deep- er cell infiltrate of similar composition extend- ed along the microvasculature, hair follicles, and sweat glands. Endothelial cells appeared plump. Immunohistochemistry demonstrated innumerable T. pallidum in the dermis. The Dermatology Reports 2010; volume 2:e2 Correspondence: G.E. Piérard, Department of Dermatopathology, CHU Sart Tilman, B-4000 Liège, Belgium. E-mail: gerald.pierard@ulg.ac.be Key words: syphilis, AIDS, immunohistochem- istry. Contributions: all authors contributed equally in the collection of clinical and histopathological information. Acknowledgements: This work was supported by a grant from the “Fonds d’Investissement de la Recherche Scientifique” of the University Hospital of Liège. No other sources of funding were used to assist in the preparation of this manuscript. The authors appreciate the excellent secretarial assistance of Mrs. Ida Leclercq and Marie Pugliese. Conflict of interest: the authors report no con- flicts of interest that are directly relevant to the content of this work. Received for publication: 19 October 2009. Revision received: 17 December 2009. Accepted for publication: 17 December 2009. This work is licensed under a Creative Commons Attribution 3.0 License (by-nc 3.0). ©Copyright P. Quatresooz et al., 2010 Licensee PAGEPress, Italy Dermatology Reports 2010; 2:e2 doi:10.4081/dr.2010.e2 Figure 1. Early syphilis. Dermal homing of T. pallidum on immunohistochemistry: (a) multiple interstitial clumps of spirochetes (200X); (b) vascular trapping of spiro- chetes (400X); (c) prominent accumulation of spirochetes in the microvasculature wall (400X). a b c No n- co mm er cia l u se on ly [Dermatology Reports 2010; 2:e2] [page 5] typical spiral, corkscrew, and threadlike spiro- chetes were highlighted by the red chromogen, and the contrast with the clear background was striking (Figure 1a, b, c). Their presence inside the lichenoid infiltrate was associated with a dense superficial and deep perivascular cuff of spirochetes. The latter slender spiro- chetes were clustered in the dermal stroma (Figure 1a) and in rims confined to the perivascular areas (Figure 1b, c). In addition, some T. pallidum were evident in the cyto- plasm of cells, particularly endothelial cells (Figure 1c). A few of these spirochetes pro- truded into the vascular lumen. None of the negative controls showed spirochete immuno - reactivity. Discussion In the present case, skin immunohisto- chemistry shed some light on the diagnosis of syphilis in an AIDS patient and showed the dermal homing and the microvascular tropism of T. pallidum. It is acknowledged that during a five-year period after inoculation, T. pallidum spreads to every organ. Then the disease is intermittently contagious. Later syphilis usual- ly becomes dormant or latent for many years. A long time later, it commonly re-emerges as a chronic and deadly illness. At any stage in its evolution, syphilis may mimic a number of other unrelated diseases. During the past decade, a sizable proportion of the population with syphilis corresponded to gay men coinfected with HIV.3,4 When the clini- cal diagnosis of syphilis is not established, a skin biopsy sometimes is submitted to the der- matopathologist without any relevant informa- tion. At the conventional histological examina- tion, the diagnostic clues for syphilis are not always obvious because the disease presenta- tion depends on both the host immunological response to the infection and the diverse angioinvasive propensity of the T. pallidum strains.5 An appropriate silver stain revealing spirochetes may remain negative or doubtful. Indeed, the histochemical silver stain may be difficult to interpret owing to heavy back- ground staining.1 Immunohistochemistry using an antibody directed to T. pallidum was reported to improve the histological diagnostic accuracy of syphilis.1,2,6,7 The present finding was assumed to illustrate the migration of T. pallidum toward the microvasculature during early syphilis. In summary, T. pallidum were abundant and heavily clustered in some specific portions of the skin. The peculiar homing of T. pallidum in the skin appears quite specific as it has not been reported for any other infectious microor- ganism. References 1. Quatresooz P, Piérard GE. Skin homing of Treponema pallidum in early syphilis. An immunohistochemical study. Appl Immu - no histochem Mol Morph 2009;17:47-50. 2. Quatresooz P, Piérard GE. Perivascular cuff and spread of Treponema pallidum. Dermatology 2009;219:259-2. 3. Frauenfelder C. Incidence of syphilis in UK rises as HIV diagnoses hold steady. Br Med J 2006;333:1089. 4. Kerani RP, Handsfield HH, Stenger MS, et al. Rising rates of syphilis in the era of syphilis elimination. Sex Transmitted Dis 2007;34:154-61. 5. Lautenschlager S. Cutaneous manifesta- tions of syphilis. Recognition and manage- ment. Am J Clin Dermatol 2006;7:291-304. 6. Hoang MP, High WA, Molberg KH. Secondary syphilis: a histologic and immu - nohistochemical evaluation. J Cutan Pathol 2004;31:595-9. 7. Buffet M, Grange PA, Gerhardt P, et al. Diagnosing Treponema pallidum in sec- ondary syphilis by PCR and immunohisto- chemistry. J Invest Dermatol 2007;127: 2345-50. Article No n- co mm er cia l u se on ly