Necrotizing fasciitis can present with skin involvement; however, it can become difficult to distinguish from the skin lesions of angioimmunoblastic T-cell lymphoma. Clostridium septicum is a common source of such infections.
1.1. Case Description
A 49-year-old man undergoing chemotherapy for angioimmunoblastic T-cell lymphoma presented with fevers, abdominal pain, and right shoulder pain. After an acute escalation in symptoms, necrotizing fasciitis with Clostridium septicum was diagnosed, primarily involving the right shoulder but with hematologic seeding. Urgent surgical debridement was performed, along with appropriately tailored antibiotic therapy. Despite aggressive treatment, the patient eventually succumbed.
While an uncommon diagnosis, necrotizing fasciitis should be kept in mind as a source of fever in the appropriate clinical context of a neutropenic patient with skin findings, fevers, and pain. A delay in diagnosis and treatment could lead a fatal outcome.
2. Keywords: Angioimmunoblastic T-Cell Lymphoma; C. septicum; Necrotizing Fasciitis; Neutropenia
We present of a case of
non-traumatic necrotizing fasciitis due to Clostridium
septicum in a 49- year old male undergoing treatment for Angioimmunoblastic
T-Cell Lymphoma (AITCL).
Necrotizing fasciitis is a
life-threatening soft tissue infection that can involve the epidermis, dermis,
subcutaneous tissue, fascia, or muscle  Factors that can predispose to
necrotizing fasciitis include penetrating traumas, surgical interventions such
as obstetrics/ gynecological procedures, non-penetrating soft-tissue injuries
such as a muscle contusion, and an immunocompromised state .
Necrotizing fasciitis is
classified as Type I or Type II. Type I is polymicrobial, contains mixed
aerobic and anaerobic organisms, and usually occurs in the elderly or in those
with underlying disease such as diabetes or
recent surgery. Type II
arises from one bacterial species and can occur independently of any predisposing
risk factors. Organisms that have been isolated from patients with necrotizing
fasciitis include Vibrio vulnificus
from those with liver cirrhosis who ingest raw oysters and C. septicum in neutropenic patients with gas gangrene. Additional
associated organisms include other Clostridium
species, Aeromonas hydrophila, and Streptococcus pyogenes [1,2].
Infection with Clostridium species, including C. perfingens, C. septicum, C. novyi,
and C. histolyticum can be due to
underlying medical conditions such as colon cancer, AIDS, hemodialysis, and
inflammatory bowel disease  It has been theorized that the bacteria enter
the blood via an ulceration or perforation in the gastrointestinal tract.
Bacteria eventually migrate through the bloodstream to the site of infection .
The patient is a 49-year
old Hispanic male who originally presented with a two-year history of waxing
and waning diffuse adenopathy that eventually became persistent. Accompanying
clinical features included splenomegaly, numerous subcutaneous nodules, and B
symptoms. Biopsies of the skin and cervical lymph nodes were consistent with
AITL. Staging evaluation demonstrated diffuse adenopathy involving the
cervical, mediastinum, bilateral hilar, retroperitoneum and mesenteric regions,
in addition to massive splenomegaly and extensive extranodal involvement
including lungs and bone marrow consistent with stage IV disease, IPI XX, PiT
Despite the extensive
burden, he presented with an excellent performance status and commenced therapy
with dose-adjusted EPOCH (Etoposide, Prednisone, Vincristine, Cyclophosphamide,
Doxorubicin) with fast clinical and excellent partial radiologic response but
kinetic failure leading to abbreviation of the cycles as soon as counts
recovered starting on cycle 2 and the addition of cyclosporine on cycle 3.
Remissions were not durable, and precluded consolidation transplant. There was
clear progression with fever and new skin lesions by cycle 5. Salvage therapy
was attempted with BV-ICE (Brentuximab vedotin, Ifosfamide, Cisplatin,
Etoposide) with no response. Romidepsin initiated as a single agent provided
fast response, but approximately 1 month later the patient progressed with
fever and skin lesions. Addition of pralatrexate led to control for another
month, but again with similar progression. While waiting for insurance approval
for lenalidomide, cyclophosphamide and prednisone were commenced with some
palliation of symptoms. He was eventually started on lenalidomide 25 mg per day
for 21 days in a 28-day cycle with dramatic response.
Approximately one month
after starting lenalidomide, the patient presented to the emergency department
with fatigue, fever, and left and right upper quadrant abdominal pain, which
had been worsening over the previous three days. He also noted the development
of a small, painful bruise at the right shoulder with no recollection of any
trauma. He was hemodynamically stable at the time of interview, except for
tachypnea. Examination revealed an ill-looking gentleman with massive
hepatosplenomegaly. Notably, skin lesions idiosyncratic for the AITL were
absent. He had a small, non-tender ecchymotic lesion at the right
supraclavicular area without palpable crepitus. Laboratory work was significant
for pancytopenia, most significantly an absolute neutrophil count of 140 cells/µL.
Chest x-ray showed fullness
of the soft tissues at the right supraclavicular fossa. Computerized tomography
(CT) of the abdomen and pelvis showed hepatosplenomegaly and intra-abdominal
adenopathy, as well as diffuse wall thickening involving the distal/terminal
ileum, cecum, and descending colon, questionable for typhlitis. Intravenous
fluids and empiric cefepime were started after blood cultures were drawn.
Within the next three hours, the ecchymotic lesion at the right shoulder rapidly
progressed to involve the neck, deltoid, upper back, and chest accompanied by
dramatically worsening pain, development of palpable crepitus, and septic shock
Repeat imaging showed
extensive emphysema in subcutaneous and deep spaces of the right neck extending
from level of lung apex to C1 vertebral body, strongly suggestive of
necrotizing fasciitis (Figure 2).
Antibiotics were escalated
to vancomycin, clindamycin, and piperacillin/tazobactam. Emergent surgical
debridement was performed. Wound and blood cultures grew C. septicum. Histopathologic analysis of excised tissue showed
mainly necrosis with bacterial colonies consistent with necrotizing fasciitis.
Growth factor support was withheld given impressive splenomegaly and potential
for splenic rupture.
Besides a large surgical
wound managed with diligent wound care, aggressive medical support led to
impressive recovery. The hallmark of his disease had been the skin lesions and
none were present for nearly one month despite being off lenalidomide. Once the
patient was stabilized in the hospital, therapy was restarted at the adjusted
dose of 10 mg/day because of severe cytopenia and kidney dysfunction. Despite
reinitiating lenalidomide, approximately 2 weeks later there was evidence of
disease not only with skin lesions but also worsening respiratory status from
progression of lung involvement by lymphoma. His condition slowly declined over
the following weeks and he succumbed two months following admission.
The patient in our case was
infected with C. septicum, a common
cause of spontaneous, nontraumatic gas gangrene. This species is described as
more aerotolerant than other clostridial organisms and more capable of
non-traumatic tissue infection [4,5] A suspicious history of C. septicum infection includes symptoms
of unbearable pain, swelling, crepitus, and bulla formation.
C. septicum is a gram-positive, anaerobic, spore-forming bacillus that can thrive
in the anaerobic environment of host tissues, where it can produce virulent
exotoxins [6,7]. The organism is found on human skin and gastrointestinal
tract. Tissue trauma and subsequent hypoxia from poor blood supply allows for
bacterial growth . Nonspontaneous gas gangrene from C. septicum is highly associated with malignancy as demonstrated by
several case reports. Colon adenocarcinoma is the most common malignancy
associated with C. septicum
infection; however, cases of lymphoma and leukemia have also been described 
One such case highlights a 49-year-old woman with acute myeloid transformation
of myelodysplastic syndrome who had undergone consolidation chemotherapy 
Another case describes a 64 year old woman with a history of chronic idiopathic
neutropenia with multifocal metastasis of C.
A literature review by
Srivastava et al. in 2017 found 94 cases of spontaneous C. septicum gas
gangrene from 1956-2016. The prognosis in these cases is grim – overall
mortality was 67%. Out of 40 cases with available information, 24 (60%)
patients died within 24 hours of admission. Of the 76 adult (>18 years old)
cases, 62 (78%) had a concurrent malignancy, 48 of which were gastrointestinal,
and 7 of which were hematological. 100% of the patients with hematological
malignancies died. Neutropenia was reported in 9/78 (11%) of cases .
Treatment for suspected
necrotizing fasciitis involves immediate surgical exploration and debridement
with broad-spectrum empiric antibiotics which may later be tailored to
sensitivities if available . For patients with neutropenia and suspected
soft tissue infection, there is a strong recommendation with high-quality evidence
by the Infectious Diseases Society of America (IDSA) for hospitalization and
empiric antibacterial therapy with vancomycin plus antipseudomonal antibiotics
such as cefepime, a carbapenem, or piperacillin-tazobactam. It is not routinely
recommended by the IDSA for adjunct colony-stimulating factor therapy,
granulocyte macrophage colony-stimulating factor, or granulocyte transfusion
for neutropenic patients in suspected soft tissue infections .
The patient in this case
had many of the published risk factors for infection with C. septicum. The purported typhilitis seen on CT imaging may have
predisposed to translocation of enteric C.
septicum across inflamed bowel mucosa, resulting in bacteremia.
Furthermore, he was immunosuppressed from the ongoing therapy with recent
steroids, which augmented his susceptibility to a catastrophic infection. In
addition, the skin lesions’ fast response to lenalidomide increased areas of
necrosis and hypoxia, predisposing to infection by C. septicum.
Lymphoma has multiple
systemic manifestations that can often obscure the clinical picture. The
aggressive B symptoms and cutaneous manifestations in our case made the
esoteric diagnosis of necrotizing fasciitis difficult to distinguish from
another flare of his disease. While undoubtedly a quite uncommon diagnosis,
given the appropriate clinical context it should be borne in mind as a
potential source of neutropenic fever. It should also be emphasized that
despite initial subtle presentation, this infection can rapidly deteriorate and
survival hinges on immediate surgical intervention and optimization of the