Disasters pile up on the rubbing heel: Sporothrix globosa as secondary infection to Mycobacterium chelonae infection

ABSTRACT

Mycobacterium chelonae and Sporothrix globosa, both of which are opportunistic pathogens, have been proved to be possible multidrug resistant. However, are all recurring symptoms in chronic infections related to decreasing susceptibility? Here we report a case of sporotrichosis secondary to M. chelonae infection. In addition, we find that the blackish-red spots under the dermoscopic view can be employed as a signal for the early identification and regression of subcutaneous fungal infection.

KEYWORDS:

• Mycobacterium chelonae
• Sporothrix globosa
• dermoscopy
• blackish-red dots
• secondary infection
• case report

Dear editor

Mycobacterium chelonae and Sporothrix globosa, both of which are opportunistic pathogens following trauma or surgical procedures, can cause chronical infection of the skin and soft tissues [1,2]. Clinical manifestations include localized papules, nodules and pustule formation, chronic ulcers or disseminated lesions in immunocompromised patients [2,3]. When their clinical presentations are atypical, it is necessary to use microbial cultivation for identification. Furthermore, both of them have also been proved to exhibit multidrug resistance in some reported cases [4,5]. Therefore, rapid modification of antimicrobials is based on drug susceptibility tests [6]. However, not all recurring symptoms in chronic infections are related to decreasing susceptibility. Here we report a case of sporotrichosis secondary to M. chelonae infection.

The patient was a 66-year-old male farmer with irregular erythematous plaques with multiple nodules and black spots on his left heel (Figure 1A). Six months ago, cutaneous infection, caused by M. chelonae, was diagnosed following skin biopsy and polymerase chain reaction sequencing analysis. Histopathology showed abundant neutrophilic infiltration, accompanied by the presence of a limited number of multinucleated giant cells and evidence of angiogenesis (see Figure S1). Acid-fast stain was positive, while periodic acid chiff (PAS) stain was negative. The PCR results using ITS1/4 and ITSC1/2 as primers for fungal detect were negative. The alignment of rpoB gene sequence showed highest identity (99.71%) with the M. chelonae [7] (GenBank accession CP041150). Although oral rifampicin 450 mg/day, moxifloxacin 400 mg/day, and clarithromycin 500 mg/day were effective initially, some reddish mass appeared at the same place after three months of treatment.

Figure 1. (A) Plaques with crusting on left heel at initial visit. (B) Dermoscopy of the lesion exhibited irregular blackish-red dots. (C) Tan velvety colonies on SDA medium and the microscopy (×400) of the slide culture at 28°C. (D) SEM showed oval conidia around hyphae in a sleeve-like arrangement (×10,000). (E) Oval dark red yeast coloured by PAS stain (×1000). (F) Black yeast by GSM stain (×400). (G) Healed heel after anti-fungal treatment. (H) Dermoscopy of healed heel showing no more blackish-red dots.

Dermoscopic view of the lesion exhibited red and yellow background, spherical and linear vessels, scales and scattered irregular blackish-red dots which had been reported before as associated with mucocutaneous fungal infections [8] (Figure 1B).

The previous diagnosis was clear, and the patient was under symptomatic therapy, but oddly his condition did not abate with time. To identify the cause of the worsening disease, tissue metagenomics next-generation sequencing (mNGS) was performed [9]. Surprisingly, the data revealed only Sporothrix globosa infection.

The scabs and secretion from the compromised skin were inoculated on Sabouraud dextrose agar (SDA) at 28°C and blood agar plates at 37°C. After 1 week, only the specimen on SDA was successfully cultured which appeared as tan velvety colonies. Microscopic examination and scanning electron microscopy of the slide culture showed oval conidia around hyphae in a sleeve-like arrangement (Figure 1C,D) which were the morphological characteristics of a Sporothrix species [10]. Corresponding to these findings, Sporothrix globosa (GenBank accession MH865636) was identified based on PCR sequencing of ITS1/4 amplicons [10]. Histopathological examination of the tissue adjacent to the black spots also detected dark red round yeast cell on PAS stain and black yeast on Gomori’s methenamine silver (GMS) stain (Figure 1E,F) while acid-fast bacteria stain was negative.

Finally, the truth came out and the current diagnosis of the patient was sporotrichosis caused by Sporothrix globosa which was the reason why the later antibacterial therapy did not yield significant results. His treatment regimen was adjusted to oral itraconazole 400 mg/day, topical naftifine-ketoconazole cream, and thermotherapy with electric blanket (topical temperature over 42°C, 60 min, once a day). Clinical improvement was observed and the patient did not report any more complications leaving acceptable scarring and the blackish-red dots progressively faded away under the dermoscopy after 4-month treatment (Figure 1G,H).

In our case, clarithromycin was initially effective in treatment, however, by 3 months into therapy, the nodules were worsening. Subsequently, the patient continued the combination medication for 6 months, but the skin lesions showed no improvement. Previous cases with developing resistance to clarithromycin after initial treatment and necessitating antibiotic adjustment have been reported [11]. But the microbiological culture results showing only Sporothrix globosa infection do not support the aforementioned possibility. To our knowledge, this is the first case of the sporotrichosis secondary to M. chelonae infection. When the skin barrier is damaged, several infections might simultaneously or sequentially occur [2,12], however, secondary infections causing similar skin lesions at the same site are relatively uncommon, adding complexity to clinical diagnosis and treatment. Therefore, multiple microbiological cultures need to be performed for accurate diagnosis and treatment when dealing with recurring cutaneous infections. We present this case to emphasize a potentiality. If anti-M. chelonae infective therapy lacks noticeable efficacy, apart from evaluating sensitivity to the prescribed antibacterials, more attention should be given to determine whether the patient has superimposed or secondary infections.

Dermoscopy is a noninvasive approach to observe the subtle characteristics of skin diseases. In previous cases, blackish-red dots have been associated with subcutaneous fungal infectious diseases [8]. In this case, we have also observed the presence of blackish-red dots, and as the disease progresses, the blackish-red dots tend to decrease. It might be connected to the elimination of fungi from the subcutaneous area to the outside of the skin, which is one of the unique defence reactions of the skin against subcutaneous fungal infections. Further skin biopsy data and properly conducted trials will be required in the future to confirm the link between this dermoscopic finding and a fungal cause of subcutaneous infection.

Acknowledgment

We thank Senior Experimentalist Chaoliang Zhang (State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University) for conducting SEM observations.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the 1.3.5 project for disciplines of excellence (ZYJC18033), and HX-Academician project (HXYS19003) of West China Hospital, Sichuan University, and the National Key Research and Development Program of China (2022YFC2504800).