- Case report
- Open Access
- Open Peer Review
A suppurative thyroiditis and perineal subcutaneous abscess related with aspergillus fumigatus: a case report and literature review
© The Author(s). 2018
- Received: 8 May 2018
- Accepted: 12 December 2018
- Published: 27 December 2018
Invasive aspergillosis is a complication in immunocompromised patients and commonly detected in patients with hematological malignancies, which mostly affect the lungs. Because of its high iodine content, rich blood supply and capsule, the thyroid is considered to be less prone to microbial invasion thus most infectious thyroiditis cases are caused by bacteria. However, a few case reports have described thyroid gland aspergilloses, most of which were due to disseminated invasive aspergillosis.
We first report a case of thyroid gland and subcutaneous labium majus aspergillosis in a Chinese patient who received long-term glucocorticoid treatment for systemic lupus erythematosus (SLE) and lupus nephritis, and then we reviewed 36 articles describing similar aspergillus infections in 41 patients.
We included 29 cases of diagnosed aspergillus thyroiditis and analyzed clinical findings, treatments and outcomes to provide clinical information for diagnosis and prognosis of thyroiditis caused by Aspergillus fumigatus.
- Aspergillus fumigatus
- Systemic lupus erythematosus
- Aspergillus thyroiditis
Aspergillus fumigatus is the most common form of aspergillus infection in humans, accounting for 70–80% of these infections . Invasive aspergillosis is an increasingly frequent opportunistic infection in immunocompromised patients such as those with an organ transplant, hematological malignancy, those receiving certain types of chemotherapy, patients infected with human immunodeficiency virus, and other types of immunosuppression therapy [2, 3]. Most often through aerosolizing, aspergillus spores first colonize the respiratory tract and related structures such as the nasopharyngeal and facial sinuses. Further immunosuppression markedly increases the risk for invasive disease characterized by tissue invasion and secondary bloodstream dissemination . The majority of thyroid aspergillosis cases are caused by disseminated invasive aspergillosis and are frequently diagnosed postmortem since they can be apparently symptomless or the clinical appearance is complicated by their comorbidities .
Epidemiology, clinical findings, and diagnostic methodology of aspergillus thyroiditis
Primary aspergillus locations
Chronic granulomatous disease
Neck erythema/ warmth
Manifestation of thyroid
Euthyroid sick syndrome
Lung-X ray/ CT
Thyroid punctured liquid/ swab/ tissue
Sputum/ airway secretion
Urine/ body fluid/ other tissue
Fine needle aspiration
Diagnostic methods and symptoms of patients
Nine patients presented with combination infections, which included bacteria, virus, non-aspergillus fungus. Fever, dyspnea, and thyroid enlargement were the most common presenting symptoms. Dyspnea was the most serious presentation in 15 patients [6–8, 11, 14, 16–18, 20, 21, 24, 25, 29, 31, 32] and caused airway obstructions in 3 patients, which led to 2 deaths [11, 20]. Dysphagia was noted in 2 patient [31, 32]. Based on the laboratory blood tests and clinical symptoms, 12 patients were proved to suffer from thyrotoxicosis [7–9, 11, 13, 15, 16, 18, 21, 30, 31, 33], and hyperthyroidism was seen in 13 cases. Most aspergillus thyroiditis cases showed signs in diagnostic imaging, but sonography and computed tomography presented nonspecific changes of thyroid gland. Histological tests (15 cases) and fine needle aspiration (15 cases) led to frequent diagnoses, but screening for aspergillus by detection of galactomannan was helpful in only 5 reports [17, 19, 21, 26, 29] (Table 1).
Treatment and survival
Almost all of the patients received glucocorticoid and/or immunosuppressive agents, but only 10 patients [7, 11, 13, 14, 17, 18, 20, 24, 31, 33] suffered from neutropenia at the moment of aspergillosis diagnosis. Furthermore, only 2 of the neutropenia patients survived [17, 18]. Aspergillus thyroiditis appeared to be a high mortality disease, even under treatment by both antifungal drugs and surgery. Altogether, 10 patients survived [8, 9, 15, 17–19, 23, 25, 27, 29] and most of them were reported in the last couple of decades except one who survived in 1972 . Six of the 10 patients had been treated with voriconazole with or without caspofungin or amphotericin B [8, 15, 17, 19, 27, 29], while only 2 of the survivors were successfully cured by amphotericin B monotherapy [9, 18]. It was remarkable that a total thyroidectomy without antifungal agents could also lead to survival in primary aspergillus thyroiditis excluding dissemination .
Probably many cases of genital involved disseminated aspergillosis were not reported, since it was a subset of cutaneous aspergillus infection. There were 7 reports of cutaneous and/or subcutaneous aspergillosis in the genital area identified in the literature [34–40]. Different from expectations, not all of the patients complained of skin lesions as the first clinical presentation. A variety of other symptoms were also revealed such as fever, perineum irritation, and difficulty in urination, defecation and sexual activity. Debridement was necessary and effective for most of the patients, while systemic antifungal administration was the cornerstone of successful treatment.
Aspergillus species are ubiquitous and can be found in soil, dust, vegetation and decaying plant material . It is the second most common cause of opportunistic fungal infection in humans after Candida albicans. It causes a severe infection in immunocompromised patients resulting in high mortality. Difficulty and delay in diagnosis and treatment often contributes to fatal outcomes. Commonly, it presents as a pulmonary infection, which invades the lung parenchyma and vasculature and later spreads to other organs. It has angioinvasive properties, which enables the fungus to disseminate via hematogenous spread.
The remarkable resistance to infection of the thyroid gland is due to its high iodine content, hydrogen peroxide production, abundant lymphatic and vascular supply, and its encapsulated location . Postmortem studies have shown that thyroid aspergillus involvement constitutes 12% of extra pulmonary disease .
Whether aspergillus thyroiditis is an infrequent disease in populations remains to be established. In our case, the patient suffered from suppurative lesions due to aspergillus fumigatus both in the thyroid gland and subcutaneous tissue in the genital area. Although fungemia was never documented, the patient most likely had disseminated aspergillosis resulting from hematogenous spread. Pulmonary involvement had a strong possibility in this case considering of the radiological manifestations, despite the lack of a positive result from respiratory specimens. It is also possible that our patient contracted the infection from colonization of adjacent tissue, such as airway, related sinuses, and skin in the genital area.
The majority of aspergillus thyroiditis cases were asymptomatic and diagnosis was primarily classified at postmortem. In fact, local signs and symptoms of fungal thyroiditis are indistinguishable from symptoms of other infectious thyroiditis. Clinical diagnosis of aspergillus thyroiditis during life continues to be a major challenge. Fine needle aspiration cytology and culture have been the most frequent and successful diagnostic tests for detecting aspergillus thyroiditis ante mortem. It also plays an important role in the diagnosis of aspergillosis involving skin and soft tissue, which could difficult to distinguish by the naked eye.
Early diagnosis of aspergillosis and the establishment of aggressive therapy before more widespread dissemination of the infection likely contributed to the successful treatment in this patient. A satisfactory outcome of invasive aspergillosis is predicated on the return of normal bone marrow function and the prompt starting of appropriate antifungal agent therapy systemically as soon as the diagnosis is established. Treatment should include the judicious use of surgical intervention as clinical circumstance may indicate. As far as our patient was concerned, drainage was effective and remained an integral component of therapy for resolution of the aspergillus abscess.
Phagocytes, particularly neutrophils, play a critical role in the host’s defense against aspergillus. Studies have demonstrated that the incidence of invasive aspergillosis is directly related to the duration of neutropenia . For disseminated disease, a reduction of immunosuppression can also help .
Amphotericin B was the mainstay of treatment for aspergillus infections even up to the 1990s, although nephrotoxicity limited its use and its efficacy was poor, especially in disseminated disease [45, 46]. Advancements in antifungal therapy have led to increased survival in patients with aspergillus infections. Voriconazole has better responses and improved survival compared to amphotericin B in invasive aspergillosis monotherapy , while caspofungin has been widely used as an effective ‘rescue’ therapy . Combination medical therapy is a subject of great interest. The synergistic effect of voriconazole and caspofungin against aspergillus is supposed to involve the simultaneous inhibition of cell membrane and cell wall biosynthesis. This suggests that a combination of voriconazole and caspofungin might reduce mortality in critically ill patients.
Aspergillus thyroiditis typically begins with a brief hyperthyroidism phase due to the release of thyroid hormone as a result of follicular cell damage. Then transient euthyroidism ensues, usually followed by hypothyroidism that ultimately recovers to euthyroidism. Therefore, the thyroid function test can show variability . Thyroid hormone levels ranged from those characteristic of hyperthyroidism to those typical of hypothyroidism. The management of thyroid hormone dysregulation is less often reported in the literature than the antifungal profile. The majority of our reviewed cases did not report the use of oral thyroid medications, and 2 cases reported that thyroid function could be normalized within 2 weeks following the initiation of antifungal therapy [9, 19]. This finding suggests that symptomatic treatment is sufficient for most patients due to the lack of thyroid-related symptomatology, even with laboratory evidence of thyroid dysfunction.
Invasive aspergillosis is a relatively frequent fungal infection occurred in immunocompromised patients, but aspergillus thyroiditis has been rarely reported. Aspergillosis involving the thyroid gland produces a high mortality rate > 60%, despite updated reports of patients treated with a novel azole, voriconazole, and an echinocandin, caspofungin. Early diagnosis of aspergillosis is a key to successful treatment. The clinicians must maintain a high level of diagnostic suspicion among those high-risk patients who present with fever and findings localized to the thyroid region or skin as well as soft tissue. Careful and thorough examinations are probably more important in those patients rather than subjective complaints, since a number of patient conditions are asymptomatic in the initial stage of invasive aspergillosis.
Consent to participate
The present study was supported by a general project from Shanghai Municipal Commission of Health and Family Planning (grant no. 2016ZB0202–01), and The Scientific Research Project supported by Huashan Hospital, Fudan University (grant no. 2014QD15).
Availability of data and materials
The datasets supporting the conclusions of this article is included within the article.
JT, JS and GW were responsible for the conception and design of the study. JT and YF were responsible for acquisition of data; furthermore, JT, YF and GW were in charge of statistical analysis. JT and GW drafted the manuscript; JS, LZ and YL revised and commented the draft, and YG, HZ and ZH read and approved the final version of the manuscript. All authors read and approved the final manuscript.
Ethics approval and consent to participate
Consent for publication
Written consent for publication was obtained from the patient.
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Barchiesi F, Mazzocato S, Mazzanti S, Gesuita R, Skrami E, Fiorentini A, Singh N. Invasive aspergillosis in liver transplant recipients: epidemiology, clinical characteristics, treatment, and outcomes in 116 cases. Liver Transpl. 2015;21(2):204–12.View ArticleGoogle Scholar
- Denning DW. Therapeutic outcome in invasive aspergillosis. Clin Infect Dis. 1996;23(3):608–15.View ArticleGoogle Scholar
- Vogeser M, Haas A, Ruckdeschel G, von Scheidt W. Steroid-induced invasive aspergillosis with thyroid gland abscess and positive blood cultures. Eur J Clin Microbiol Infect Dis. 1998;17(3):215–6.View ArticleGoogle Scholar
- Bartlett JG. Aspergillosis update. Medicine. 2000;79(4):281–2.View ArticleGoogle Scholar
- Nguyen J, Manera R, Minutti C. Aspergillus thyroiditis: a review of the literature to highlight clinical challenges. Eur J Clin Microbiol Infect Dis. 2012;31(12):3259–64.View ArticleGoogle Scholar
- Gowing NF, Hamlin IM. Tissue reactions to aspergillus in cases of Hodgkin's disease and leukaemia. J Clin Pathol. 1960;13:396–413.View ArticleGoogle Scholar
- Badawy SM, Becktell KD, Muller WJ, Schneiderman J. Aspergillus thyroiditis: first antemortem case diagnosed by fine-needle aspiration culture in a pediatric stem cell transplant patient. Transpl Infect Dis. 2015;17(6):868–71.View ArticleGoogle Scholar
- Chung S, Lee JH, Lim Y, Yang HK, Chang YS. Isolated aspergillus thyroiditis in an immunocompromised patient. NDT plus. 2010;3(6):597–8.PubMedPubMed CentralGoogle Scholar
- Halazun JF, Anast CS, Lukens JN. Thyrotoxicosis associated with aspergillus thyroiditis in chronic granulomatous disease. J Pediatr. 1972;80(1):106–8.View ArticleGoogle Scholar
- Keane WM, Potsic WP, Perloff LJ, Barker CF, Grossman RA. Aspergillus thyroiditis. Otolaryngology. 1978;86(5):ORL–761-5.View ArticleGoogle Scholar
- Kishi Y, Negishi M, Kami M, Hamaki T, Miyakoshi S, Ueyama J, Morinaga S, Mutou Y. Fatal airway obstruction caused by invasive aspergillosis of the thyroid gland. Leuk Lymphoma. 2002;43(3):669–71.View ArticleGoogle Scholar
- Lisbona R, Lacourciere Y, Rosenthall L. Aspergillomatous abscesses of the brain and thyroid. J Nucl Med. 1973;14(7):541–2.PubMedGoogle Scholar
- Marui S, de Lima Pereira AC, de Araujo Maia RM, Borba EF. Suppurative thyroiditis due to aspergillosis: a case report. J Med Case Rep. 2014;8:379.View ArticleGoogle Scholar
- Santiago M, Martinez JH, Palermo C, Figueroa C, Torres O, Trinidad R, Gonzalez E, Miranda Mde L, Garcia M, Villamarzo G. Rapidly growing thyroid mass in an immunocompromised young male adult. Case Rep Endocrinol. 2013;2013:290843.PubMedPubMed CentralGoogle Scholar
- Solak Y, Atalay H, Nar A, Ozbek O, Turkmen K, Erekul S, Turk S. Aspergillus thyroiditis in a renal transplant recipient mimicking subacute thyroiditis. Transpl Infect Dis. 2011;13(2):178–81.View ArticleGoogle Scholar
- Torres AM, Agrawal S, Peters S, Khurana K, Feiglin D, Schroeder E, Izquierdo R. Invasive aspergillosis diagnosed by fine-needle aspiration of the thyroid gland. Thyroid. 1999;9(11):1119–22.View ArticleGoogle Scholar
- Zwitserloot AM, Warris A, van't Hek LG, van Die LE, Verweij PE, Mavinkurve-Groothuis AM. Disseminated aspergillosis in an adolescent with acute lymphoblastic leukemia. Pediatr Blood Cancer. 2008;51(3):423–6.View ArticleGoogle Scholar
- Kim SH, Kim JY, Park WC, Kim MK, Kim TJ. Sequential sonographic features of primary invasive aspergillosis involving only the thyroid gland: a case report and literature review. Iran J Radiol. 2016;13(1):e27890.PubMedPubMed CentralGoogle Scholar
- Ataca P, Atilla E, Saracoglu P, Yilmaz G, Civriz Bozdag S, Toprak SK, Yuksel MK, Ceyhan K, Topcuoglu P. Aspergillus thyroiditis after allogeneic hematopoietic stem cell transplantation. Case Rep Hematol. 2015;2015:537187.PubMedPubMed CentralGoogle Scholar
- Cornet M, Ugo V, Lefort E, Molina T, James JM, Vekhoff A, Audouin J, Marie JP, Bouvet A. A case of disseminated aspergillosis with thyroid involvement. Eur J Clin Microbiol Infect Dis. 2001;20(5):358–9.PubMedGoogle Scholar
- Hornef MW, Schopohl J, Zietz C, Hallfeldt KK, Roggenkamp A, Gartner R, Heesemann J. Thyrotoxicosis induced by thyroid involvement of disseminated aspergillus fumigatus infection. J Clin Microbiol. 2000;38(2):886–7.PubMedPubMed CentralGoogle Scholar
- Matsui Y, Sugawara Y, Tsukada K, Kishi Y, Shibahara J, Makuuchi M. Aspergillus thyroiditis in a living donor liver transplant recipient. J Infect. 2006;53(6):e231–3.View ArticleGoogle Scholar
- Thada ND, Prasad SC, Alva B, Pokharel M, Prasad KC. A rare case of suppurative aspergillosis of the thyroid. Case Rep Otolaryngol. 2013;2013:956236.PubMedPubMed CentralGoogle Scholar
- Winzelberg GG, Gore J, Yu D, Vagenakis AG, Braverman LE. Aspergillus flavus as a cause of thyroiditis in an immunosuppressed host. Johns Hopkins Med J. 1979;144(3):90–3.PubMedGoogle Scholar
- Erdem H, Uzunlar AK, Yildirim U, Yildirim M, Geyik MF. Diffuse infiltration of aspergillus hyphae in the thyroid gland with multinodular goiter. Indian J Pathol Microbiol. 2011;54(4):814–6.PubMedGoogle Scholar
- Elzi L, Laifer G, Bremerich J, Vosbeck J, Mayr M. Invasive apergillosis with myocardial involvement after kidney transplantation. Nephrol Dial Transplant. 2005;20(3):631–4.View ArticleGoogle Scholar
- Guetgemann A, Brandenburg VM, Ketteler M, Riehl J, Floege J. Unclear fever 7 weeks after renal transplantation in a 56-year-old patient. Nephrol Dial Transplant. 2006;21(8):2325–7.View ArticleGoogle Scholar
- Solary E, Rifle G, Chalopin JM, Rifle-Mediavilla C, Rebibou JM, Camerlynck P, Justrabo E, Cuisenier B, Caillot D, Mousson C, et al. Disseminated aspergillosis revealed by thyroiditis in a renal allograft recipient. Transplantation. 1987;44(6):839–40.View ArticleGoogle Scholar
- Cicora F, Mos F, Paz M, Roberti J. Successful treatment of acute thyroiditis due to aspergillus spp. in the context of disseminated invasive aspergillosis in a kidney transplant patient. Nefrologia. 2013;33(4):618–9.PubMedGoogle Scholar
- Jang KS, Han HX, Oh YH, Paik SS. Aspergillosis of the thyroid gland diagnosed by fine needle aspiration cytology. Acta Cytol. 2004;48(6):875–6.PubMedGoogle Scholar
- Alvi MM, Meyer DS, Hardin NJ, Dekay JG, Marney AM, Gilbert MP. Aspergillus thyroiditis: a complication of respiratory tract infection in an immunocompromised patient. Case Rep Endocrinol. 2013;2013:741041.PubMedPubMed CentralGoogle Scholar
- Sion ML, Armenaka MC, Georgiadis I, Paraskevopoulos G, Nikolaidis I. Aspergillus fumigatus abscesses of the thyroid with obstruction of the esophagus. Thyroid. 2004;14(9):786–8.View ArticleGoogle Scholar
- Ayala AR, Basaria S, Roberts KE, Cooper DS. Aspergillus thyroiditis. Postgrad Med J. 2001;77(907):336.View ArticleGoogle Scholar
- Arikan S, Uzun O, Cetinkaya Y, Kocagoz S, Akova M, Unal S. Primary cutaneous aspergillosis in human immunodeficiency virus-infected patients: two cases and review. Clin Infect Dis. 1998;27(3):641–3.View ArticleGoogle Scholar
- Chen Z, Li HM, Han W, Sang JH, Du J, Zhang WJ, Zhang JZ. Genital cutaneous lesions in an allogeneic haematopoietic stem-cell transplant recipient with aspergillosis. Clin Exp Dermatol. 2009;34(4):556–8.View ArticleGoogle Scholar
- Davido HT, Ryndin I, Kohler TS, Hadegard W, Monga M, Fung L. Aspergillosis of the scrotum: non-surgical management. Int J Urol. 2007;14(2):164–6.View ArticleGoogle Scholar
- Powell CR, Allshouse M, Bethel KJ, Mevorach RA. Invasive aspergillosis of the scrotum. J Urol. 1998;159(4):1306–8.View ArticleGoogle Scholar
- Raszka WV Jr, Shoupe BL, Edwards EG. Isolated primary cutaneous aspergillosis of the labia. Med Pediatr Oncol. 1993;21(5):375–8.View ArticleGoogle Scholar
- Li BK, Wang X, Ding Q. A case report of severe aspergillus flavus penile infection. Asian J Androl. 2009;11(5):638–40.View ArticleGoogle Scholar
- Tahir C, Garbati M, Nggada HA, Yawe EH, Abubakar AM. Primary cutaneous aspergillosis in an immunocompetent patient. J Surg Tech Case Rep. 2011;3(2):94–6.View ArticleGoogle Scholar
- Walsh TJ, Pizzo PA. In: Hoeprich PD, Jordan C, Ronald AR, editors. Aspergillosis. In: infectious diseases. 5th edn. Philadelphia: Lippincott; 1994. p. 541–7.Google Scholar
- Pearce EN, Farwell AP, Braverman LE. Thyroiditis. N Engl J Med. 2003;348(26):2646–55.View ArticleGoogle Scholar
- Hori A, Kami M, Kishi Y, Machida U, Matsumura T, Kashima T. Clinical significance of extra-pulmonary involvement of invasive aspergillosis: a retrospective autopsy-based study of 107 patients. J Hosp Infect. 2002;50(3):175–82.View ArticleGoogle Scholar
- Saral R. Candida and Aspergillus infections in immunocompromised patients: an overview. Rev Infect Dis. 1991;13(3):487–92.View ArticleGoogle Scholar
- Denning DW, Stevens DA. Antifungal and surgical treatment of invasive aspergillosis: review of 2,121 published cases. Rev Infect Dis. 1990;12(6):1147–201.View ArticleGoogle Scholar
- Ostrosky-Zeichner L, Marr KA, Rex JH, Cohen SH. Amphotericin B: time for a new “gold standard”. Clin Infect Dis. 2003;37(3):415–25.View ArticleGoogle Scholar
- Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, Kern WV, Marr KA, Ribaud P, Lortholary O, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002;347(6):408–15.View ArticleGoogle Scholar
- Maertens J, Raad I, Petrikkos G, Boogaerts M, Selleslag D, Petersen FB, Sable CA, Kartsonis NA, Ngai A, Taylor A, et al. Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy. Clin Infect Dis. 2004;39(11):1563–71.View ArticleGoogle Scholar