Cutaneous Mycobacterium haemophilum infection with jarisch–herxheimer reaction: A case report from Taiwan

Chi-Hui Wang; Chun-Wei Lu; Yun Fu; Ting-Shu Wu; Chin-Fang Lu; Hong-Shang Hong

doi:10.4103/ds.ds_7_19

CASE REPORT

Year : 2019 | Volume : 37 | Issue : 4 | Page : 229-232

Cutaneous Mycobacterium haemophilum infection with jarisch–herxheimer reaction: A case report from Taiwan

Chi-Hui Wang¹, Chun-Wei Lu², Yun Fu¹, Ting-Shu Wu³, Chin-Fang Lu⁴, Hong-Shang Hong¹
¹ Department of Dermatology, Chang Gung Memorial Hospital, Linkou, Taipei, Taiwan
² Department of Dermatology, Chang Gung Memorial Hospital, Linkou, Taipei; Department of Medicine, College of Medicine; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan, Taiwan
³ Department of Internal Medicine, Division of Infectious Diseases, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
⁴ Department of Dermatology, Research Center of Cutaneous Disorders, Chung Shan Hospital, Taipei, Taiwan

Date of Submission	19-Sep-2018
Date of Decision	20-Feb-2019
Date of Acceptance	30-Mar-2019
Date of Web Publication	16-Dec-2019

Correspondence Address:
Dr. Hong-Shang Hong
No. 199, Dunhua N. Road., Songshan District, Taipei City 105
Taiwan

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ds.ds_7_19

Abstract

Mycobacterium haemophilum is a slow-growing and iron-dependent nontuberculous mycobacterium that can cause cutaneous ulcerations or nodular lesions. The diagnosis of cutaneous M. haemophilum infection is currently extremely rare in Taiwan. An 80-year-old Chinese man taking oral prednisolone for months presented with multiple erythematous as well as indurated and painful nodules over his right forearm. The diagnosis of M. haemophilum infection was confirmed through positive acid-fast staining – a technique used in histopathology and species identification – which was performed using molecular methods. Notably, Jarisch–Herxheimer reaction developed promptly during the antimicrobial therapy. Ideal skin culture conditions and specific molecular identification techniques are required for optimal detection of M. haemophilum.

Keywords: Cutaneous infection, Jarisch–Herxheimer reaction, Mycobacterium haemophilum

How to cite this article:
Wang CH, Lu CW, Fu Y, Wu TS, Lu CF, Hong HS. Cutaneous Mycobacterium haemophilum infection with jarisch–herxheimer reaction: A case report from Taiwan. Dermatol Sin 2019;37:229-32

How to cite this URL:
Wang CH, Lu CW, Fu Y, Wu TS, Lu CF, Hong HS. Cutaneous Mycobacterium haemophilum infection with jarisch–herxheimer reaction: A case report from Taiwan. Dermatol Sin [serial online] 2019 [cited 2023 May 31];37:229-32. Available from: https://www.dermsinica.org/text.asp?2019/37/4/229/273102

Introduction

Cutaneous Mycobacterium haemophilum infection is a rare clinical manifestation in Taiwan, which is diagnosed mainly by using tissue cultures. Jarisch–Herxheimer reaction (JHR) was previously considered to be a paradoxical reaction and a component of transient immunological response that occurs in patients who have received antisyphilis therapy. However, it is also observed in patients with infections such as systemic fungal infection and Lyme disease. In the present study, we present a case of cutaneous M. haemophilum infection with the JHR identified in Taiwan.

Case Report

An 80-year-old Chinese man with a background of benign prostate hyperplasia and hypertension presented with multiple erythematous and indurated nodules over his right forearm persisting for 1 month. The patient was an agricultural worker who had a history of trauma involving irritant contact dermatitis caused by insecticide agents 3 months previously. He had been taking prednisolone (10 mg/day) as a long-term prescription from a physician at an outside institution since then. The manifestation of erythema and swelling of the skin that diagnosed as a reaction to irritants on his right arm subsided gradually, whereas several reddish and firm nodules developed 2 months later. Notably, the nodular lesions began distally on his right wrist and spread proximally. A skin examination in the outpatient department revealed multiple severe erythematous and indurated nodules measuring up to 1.2 cm, with sporotrichoid that was accompanied by a painful sensation spreading across his forearm [Figure 1]a and [Figure 1]b. An incision and drainage procedure for the yellowish nodules was performed and assisted in draining the contents of the purulent abscesses. Tissue from an excisional biopsy of one of the nodules was sent for histology and microbial cultures (bacterial, fungal, and mycobacterial cultures).

Figure 1: (a) Multiple erythematous and indurated nodules with sporotrichoid spreading across the right dorsal hand to the forearm. (b) Redness in the nodular lesions on the ulnar side of the forearm. Some nodules developed purulent contents. (c) Histopathology of an erythematous nodule on the right forearm revealed abscess cavities surrounded by dermal granulomatous inflammation (H and E, ×20). (d) The granuloma with infiltration of histiocytes, lymphocytes, plasma cells, and neutrophils (H and E, ×200). (e) Abundant acid-fast bacilli were observed in the histopathology through Ziehl–Neelsen staining (×400)

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Hematoxylin and eosin staining of the biopsy revealed that the abscess cavities were both surrounded by granulomatous inflammation in the superficial and mid-dermis [Figure 1]c and interspersed with an admixture of inflammatory cells, including histiocytes, lymphocytes, plasma cells, and scattered neutrophils [Figure 1]d. Occasional multinucleated giant cells were also observed. Ziehl–Neelsen staining of the histopathology lesions revealed an abundance of acid-fast bacilli [Figure 1]e. A periodic acid–Schiff stain yielded negative results. The histopathological findings suggested suppurative granulomatous inflammation with possible nontuberculous mycobacterial infection.

Initially, the patient was treated with moxifloxacin (400 mg/day) and clarithromycin (1000 mg/day) with regular monitoring through electrocardiogram (ECG) tests. A follow-up ECG measured after 2 weeks revealed an abnormally prolonged QTc interval, and an alternative regimen of trimethoprim–sulfamethoxazole (1600 mg/day) and clarithromycin (1000 mg/day) was subsequently administered. Within 24 h, the patient exhibited a spiked fever reaching 38.9°C, arthralgia, and progressive swelling of multiple painful and erythematous nodules on his right forearm [Figure 2]a. Laboratory data indicated that his white blood cell count was 11,800/μL segmented 91%) and that he had a significantly elevated level of C-reactive protein (146.82 mg/L). The JHR was suspected on the basis of the clinical presentation, and a 7-day course of prednisolone (10 mg twice daily) was prescribed for its anti-inflammatory effects, which showed a favorable treatment response without recurrence. A rebiopsy of tender erythematous nodules was also performed for a detailed survey. Numerous acid-fast-positive bacilli were still observed microscopically in the tissue, but the bacilli exhibited marked degeneration.

Figure 2: (a) Worsened swelling and tenderness of the cutaneous lesions on the right forearm. (b) Resolved skin lesions upon follow-up

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Routine bacterial and fungal cultures of tissues from the biopsy specimen of the nodules remained negative throughout the incubation. However, mycobacterial cultures finally yielded positive results on chocolate blood agar at 30°C following 17 days of incubation. Matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI-TOF MS) performed on the isolates identified the Mycobacterium species as M. haemophilum. Consequently, the oral regimen consisting of rifabutin (150 mg/day) and clarithromycin (1000 mg/day) was administered as a combined antimicrobial therapy. The induration of erythematous subcutaneous nodules on his right forearm significantly reduced after 2 months of treatment. Until now, the patient has received regular antimycobacterial medication. The majority of the firm nodules on his right forearm have softened and subsided without the formation of new skin lesions [Figure 2]b.

Discussion

M. haemophilum, or the “blood-loving” mycobacterium, is a slow-growing acid-fast bacillus that differs from all other identified Mycobacterium species in that it favors a lower growth temperature between 30°C and 32°C and exhibits a unique culture requirement for iron supplementation.^[1],[2] To date, only roughly 100 cases of cutaneous M. haemophilum infection have been reported worldwide. Only one case has ever been reported in Taiwan, which involved the development of an M. haemophilum infection in a scratch wound on the lower leg.^[3] Based on published studies, two groups have been identified as being at primary risk for M. haemophilum infection, namely immunocompromised patients, in whom M. haemophilum develops as an opportunistic infection, and healthy children, who typically present with cervical lymphadenitis.^[2] In view of cutaneous M. haemophilum infection, it mainly occurs in immunosuppressive patients, which have been especially reported in individuals with lymphoma, HIV, organ transplant, and autoimmune disorders on immune modulation.^[2],[4]

The clinical manifestations of cutaneous infections caused by M. haemophilum appear to encompass a broad spectrum, ranging from localized lesions, such as erythematous papuloplaques, necrotic abscesses, and chronic ulcers, to systemic diseases with cutaneous dissemination.^[5] Cutaneous lesions tend to occur on cooler body parts, such as extremities.^[6]M. haemophilum skin infections often mimic Mycobacterium marinum infections. However, in contrast to M. marinum infections, M. haemophilum infections produce painful nodular lesions and a unique pattern of sporotrichoid spreading.^[7]

The histologic spectrum of M. haemophilum infections appears parallel to those of most other mycobacterial infections, which are characterized by granulomatous or mixed suppurative and granulomatous reactions.^[7],[8] Bacilli can be detected both intracellularly and extracellularly in varying amounts in the affected tissue. Microbiologically, the culturing of M. haemophilum is most frequently conducted by measuring the assimilation of bacteria in a broth medium. The combination of a liquid culture with a solid medium is recommended. Löwenstein–Jensen egg-based media and solid agar-based media, such as Middlebrook 7H11 agars, are commercially obtainable; however, hemin-supplemented media, such as chocolate agar, should be used for growth.^[9] Molecular identification methods – such as MALDI-TOF MS and pyrosequencing – a new-generation sequencing method – have been utilized for the differentiation of nontuberculous Mycobacterium species.^{[2],[10],[11]}

No standard guidelines have yet been established for the antimicrobial therapy of M. haemophilum. Generally, experts agree that patients should be prescribed multiple antibiotics comprising a combination of clarithromycin, ciprofloxacin, and one of the rifamycins.^{[1],[12],[13]} The duration and amount of treatment depend on the cutaneous manifestation, degree of immunosuppression, and clinical course; the length of the treatment may be 12–24 months.^[12],[14] Moreover, various factors may affect treatment, such as adverse reactions to antibiotics, inability to reduce immunosuppressive agents, and superinfection of skin lesions.^[15]

Notably, the patient exhibited spiked fever, myalgia, and exacerbation of preexisting symptoms, with swelling and tenderness of the skin lesions 1 day after the administration of alternative antimicrobial agents. The rapid worsening following antibiotic treatment was diagnosed as a JHR. The JHR is a transient immunological phenomenon commonly observed in patients receiving antitreponemal therapy. The prevailing theory surrounding the etiology of the JHR implicates endotoxin-like substances and cytokine elevation as causal factors.^[16] The underlying pathophysiologic mechanisms postulate that massive phagocytosis by macrophages results in the release and temporary elevation of pyrogenic cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-6, thus causing the exacerbating relevant symptoms of JHR.^[17] Meanwhile, the similar interaction of macrophages and differential induction of pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, are thought to introduce an effective innate antimycobacterial immune response.^[18]

Clinically, the JHR manifests as short-term constitutional symptoms including fever, chills, myalgia, and deterioration of existing cutaneous lesions, which often appears within 24 h after initiating the antibiotic treatment. The JHR is generally a self-contained condition that can be managed symptomatically. Timely administration of certain established medications (e.g., corticosteroids) before that of antimicrobial agents can offset the development of a severe JHR.^[17] A review of relevant literature led to the discovery of a report of M. tuberculosis cervical lymphadenitis manifesting as ocular JHR following the initiation of antituberculous therapy, which resulted in prompt resolution by administering oral prednisolone (25 mg once daily).^[19] In our case, the febrile status and progressive tenderness of the skin lesions also subsided rapidly under the treatment of systemic corticosteroids.

Conclusion

This study presents a case of cutaneous M. haemophilum infection complicated with a JHR that occurred in an unusual situation of a patient receiving an immunosuppressive drug for the treatment of skin inflammation rather than organ transplantation. Increased clinical suspicion, specific histopathological examinations, and a targeted survey conducted with optimal culture settings and molecular identification techniques were crucial for the early diagnosis of M. haemophilum.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest

References

1.	Saubolle MA, Kiehn TE, White MH, Rudinsky MF, Armstrong D. Mycobacterium haemophilum: Microbiology and expanding clinical and geographic spectra of disease in humans. Clin Microbiol Rev 1996;9:435-47.
2.	Lindeboom JA, Bruijnesteijn van Coppenraet LE, van Soolingen D, Prins JM, Kuijper EJ. Clinical manifestations, diagnosis, and treatment of Mycobacterium haemophilum infections. Clin Microbiol Rev 2011;24:701-17.
3.	Hsiao CH, Tsai TF, Hsueh PR. Characteristics of skin and soft tissue infection caused by non-tuberculous mycobacteria in Taiwan. Int J Tuberc Lung Dis 2011;15:811-7.
4.	Tyner HL, Wilson JW. Fifteen-year clinical experience with Mycobacterium haemophilum at the Mayo Clinic: A case series. J Clin Tuberc Other Mycobact Dis 2017;8:26-32.
5.	Geisler WM, Harrington RD, Wallis CK, Harnisch JP, Liles WC. Broad spectrum of dermatologic manifestations caused by Mycobacterium haemophilum infection. Arch Dermatol 2002;138:229-30.
6.	Gao W, Chen H, Wang H, Jiang H, Liu W, Hao D, et al. Bilateral sporotrichoid cutaneous infection by Mycobacterium haemophilum in a Chinese patient with systemic lupus erythematosus. Acta Derm Venereol 2015;95:760-1.
7.	Busam KJ, Kiehn TE, Salob SP, Myskowski PL. Histologic reactions to cutaneous infections by Mycobacterium haemophilum. Am J Surg Pathol 1999;23:1379-85.
8.	Fariña MC, Gegundez MI, Piqué E, Esteban J, Martín L, Requena L, et al. Cutaneous tuberculosis: A clinical, histopathologic, and bacteriologic study. J Am Acad Dermatol 1995;33:433-40.
9.	Atlas RM, Snyder. JW. Handbook of Media for Clinical Microbiology. 2^nd ed. Taylor & Francis Group; Boca Raton; 2006. p. 307.
10.	Pai R, Limor J, Beall B. Use of pyrosequencing to differentiate Streptococcus pneumoniae serotypes 6A and 6B. J Clin Microbiol 2005;43:4820-2.
11.	Lotz A, Ferroni A, Beretti JL, Dauphin B, Carbonnelle E, Guet-Revillet H, et al. Rapid identification of mycobacterial whole cells in solid and liquid culture media by matrix-assisted laser desorption ionization-time of flight mass spectrometry. J Clin Microbiol 2010;48:4481-6.
12.	Shah MK, Sebti A, Kiehn TE, Massarella SA, Sepkowitz KA. Mycobacterium haemophilum in immunocompromised patients. Clin Infect Dis 2001;33:330-7.
13.	Wu ML, Aziz DB, Dartois V, Dick T. NTM drug discovery: Status, gaps and the way forward. Drug Discov Today 2018;23:1502-19.
14.	Tangkosakul T, Hongmanee P, Malathum K. Cutaneous Mycobacterium haemophilum infections in immunocompromised patients in a tertiary hospital in Bangkok, Thailand: Under-reported/under-recognized infection. JMM Case Rep 2014;1:e002618.
15.	Oh CC, Pang SM, Busmanis I, Sun S, Sng LH. Mycobacterium haemophilum in an elderly Chinese woman. Int J Dermatol 2014;53:1129-32.
16.	Pound MW, May DB. Proposed mechanisms and preventative options of Jarisch-Herxheimer reactions. J Clin Pharm Ther 2005;30:291-5.
17.	Belum GR, Belum VR, Chaitanya Arudra SK, Reddy BS. The Jarisch-Herxheimer reaction: Revisited. Travel Med Infect Dis 2013;11:231-7.
18.	Singh PP, Goyal A. Interleukin-6: A potent biomarker of mycobacterial infection. Springerplus 2013;2:686.
19.	Cheung CM, Chee SP. Jarisch-Herxheimer reaction: Paradoxical worsening of tuberculosis chorioretinitis following initiation of antituberculous therapy. Eye (Lond) 2009;23:1472-3.