primary cutaneous aspergillosis in an acutely

1
The Case: Our patient was an 81 year old lady with right upper lobe NSCLC – initially diagnosed 1 st Jan 2018 (stage IIIA), treated curatively with radical radiotherapy in March 2018, but had significant disease progression in her chest in November 2018. She wasn’t fit enough (poor Performance Status 2) so could not have palliative chemotherapy and presented with SVC obstruction secondary to invasion of cancer and was stented 19 th March 2019. At that time she was started on a reducing course of Dexamethasone from 8mg to 2mg from March to April and placed onto anticoagulation (warfarin). She was admitted to the Dermatology ward in mid-April with acutely erythematous and necrotic right arm with progressing ulcer (A, B) after her initial presenting complaint of shortness of breath and recent partial- thickness burn from spilling her tea (forearm and upper chest/shoulder involved) A biopsy was taken with the differential of pyoderma, necrotic and infected burn or warfarin-induced necrosis. She was treated with antibiotics initially but the ulcer eroded further with arterial bleeding, her clinical picture worsened, and she was palliatively discharged to Marie Curie Hospice for end of life care. She subsequently passed away. The Histology: Results came back after the patient was discharged and showed a “neutrophilic dermatitis with fibrinoid necrosis (C – white arrow) and deep fungal infection (D, red arrow) with features in keeping with aspergillosis.”(C,D) There is dense neutrophil rich inflammation (C – blue arrow) affecting the entire dermis and focally extend into the subcutaneous fat. Secondary vasculitis with fibrinoid necrosis is seen within the area of inflammation. Classification of fungal organism on H+E morphology is prone to error. Commonly quoted as being “multi-septate with acute-angle branching” (D) No culture was obtained to confirm fungal species type. Further information on Primary Cutaneous Aspergillosis (PCA) and Dexamethasone: Typically the fungus is introduced through a wound (cannula, dressing, surgery). Common risk factors for PCA are haematological malignancy, solid organ transplantation, HIV, burns, high- dose steroids, Neutropenic hosts develop infection characterized by extensive angioinvasion, haemorrhagic thrombosis and necrosis with a high fungal burden. Glucocorticoid-immunosuppressed hosts present with infection dominated by extensive necrosis, less angioinvasion, and a lower fungal burden suggestive of an inflammation-driven pathology (1) The mechanism by which Dexamethasone allows PCA is possibly that macrophages lose their ability to prevent Aspergillus fumigatus germination – allowing accelerated fungal growth, destruction of macrophages, and induction of an anti-inflammatory cytokine profile. (2) Voriconazole has the best evidence for highest survival rate (70.8%), vs liposomal Amphotericin B (57.9%) (3) Primary Cutaneous Aspergillosis in an Acutely Immunocompromised Patient Dr Matthew Alexander (Registrar) and Dr Batoul Nasr (Consultant) – Royal Victoria Infirmary – NE1 4LP Take-home messages: Risk factors in this case were: high-dose steroid (Dexamethasone) and a skin injury (burn from hot drink) Primary cutaneous aspergillosis has a high mortality rate (31.5-35.7%) (4) References: 1. Russell E. Lewis, Dimitrios P. Kontoyiannis, Invasive aspergillosis in glucocorticoid-treated patients, Medical Mycology, Volume 47, Issue Supplement_1, 2009, Pages S271–S281, 2. Luvanda, M.K.; Posch, W.; Vosper, J.; Zaderer, V.; Noureen, A.; Lass-Flörl, C.; Wilflingseder, D. Dexamethasone Promotes Aspergillus fumigatus Growth in Macrophages by Triggering M2 Repolarization via Targeting PKM2. J. Fungi 2021, 7, 70. 3. Voriconazole versus Amphotericin B for Primary Therapy of Invasive Aspergillosis N Engl J Med 2002; 347:408-415 DOI: 10.1056/NEJMoa020191 4. Alexander M. Tatara, Antonios G. Mikos, and Dimitrios P. Kontoyiannis. Factors affecting patient outcome in primary cutaneous aspergillosis. Medicine 2016 Jun; 95(26): e3747 Culture is best for definitive diagnosis as histology is prone to error: A B C D

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Page 1: Primary Cutaneous Aspergillosis in an Acutely

The Case:• Our patient was an 81 year old lady with right upper lobe

NSCLC – initially diagnosed 1st Jan 2018 (stage IIIA), treated curatively with radical radiotherapy in March 2018, but had significant disease progression in her chest in November 2018.

• She wasn’t fit enough (poor Performance Status 2) so could not have palliative chemotherapy and presented with SVC obstruction secondary to invasion of cancer and was stented 19th March 2019.

• At that time she was started on a reducing course of Dexamethasone from 8mg to 2mg from March to April and placed onto anticoagulation (warfarin).

• She was admitted to the Dermatology ward in mid-April with acutely erythematous and necrotic right arm with progressing ulcer (A, B) after her initial presenting complaint of shortness of breath and recent partial-thickness burn from spilling her tea (forearm and upper chest/shoulder involved)

• A biopsy was taken with the differential of pyoderma, necrotic and infected burn or warfarin-induced necrosis.

• She was treated with antibiotics initially but the ulcer eroded further with arterial bleeding, her clinical picture worsened, and she was palliatively discharged to Marie Curie Hospice for end of life care. She subsequently passed away.

The Histology:• Results came back after the patient was discharged and

showed a “neutrophilic dermatitis with fibrinoid necrosis(C – white arrow) and deep fungal infection (D, redarrow) with features in keeping with aspergillosis.”(C,D)

• There is dense neutrophil rich inflammation (C – bluearrow) affecting the entire dermis and focally extend intothe subcutaneous fat. Secondary vasculitis with fibrinoidnecrosis is seen within the area of inflammation.

• Classification of fungal organism on H+E morphology isprone to error. Commonly quoted as being “multi-septatewith acute-angle branching” (D)

• No culture was obtained to confirm fungal species type.

Further information on Primary Cutaneous Aspergillosis (PCA) and Dexamethasone:• Typically the fungus is introduced through a wound

(cannula, dressing, surgery).• Common risk factors for PCA are haematological

malignancy, solid organ transplantation, HIV, burns, high-dose steroids,

• Neutropenic hosts develop infection characterized byextensive angioinvasion, haemorrhagic thrombosis andnecrosis with a high fungal burden.

• Glucocorticoid-immunosuppressed hosts present withinfection dominated by extensive necrosis, lessangioinvasion, and a lower fungal burden suggestive ofan inflammation-driven pathology (1)

• The mechanism by which Dexamethasone allows PCA ispossibly that macrophages lose their ability toprevent Aspergillus fumigatus germination – allowingaccelerated fungal growth, destruction of macrophages,and induction of an anti-inflammatory cytokine profile.(2)

• Voriconazole has the best evidence for highest survivalrate (70.8%), vs liposomal Amphotericin B (57.9%) (3)

Primary Cutaneous Aspergillosis in an Acutely Immunocompromised Patient Dr Matthew Alexander (Registrar) and Dr Batoul Nasr (Consultant) – Royal Victoria Infirmary – NE1 4LP

Take-home messages:• Risk factors in this case were: high-dose steroid

(Dexamethasone) and a skin injury (burn from hot drink)• Primary cutaneous aspergillosis has a high mortality rate

(31.5-35.7%) (4)

References:1. Russell E. Lewis, Dimitrios P. Kontoyiannis, Invasive aspergillosis in

glucocorticoid-treated patients, Medical Mycology, Volume 47, Issue

Supplement_1, 2009, Pages S271–S281,

2. Luvanda, M.K.; Posch, W.; Vosper, J.; Zaderer, V.; Noureen, A.; Lass-Flörl, C.;

Wilflingseder, D. Dexamethasone Promotes Aspergillus fumigatus Growth in

Macrophages by Triggering M2 Repolarization via Targeting PKM2. J.

Fungi 2021, 7, 70.

3. Voriconazole versus Amphotericin B for Primary Therapy of Invasive

Aspergillosis N Engl J Med 2002; 347:408-415 DOI: 10.1056/NEJMoa020191

4. Alexander M. Tatara, Antonios G. Mikos, and Dimitrios P. Kontoyiannis. Factors

affecting patient outcome in primary cutaneous aspergillosis. Medicine 2016

Jun; 95(26): e3747

• Culture is best for definitive diagnosis as histologyis prone to error:

A

B

C D