By
Yomna Mazid El-Hamd
Assist. Lecturer
A -20- y old male patient.
Solitary painful skin lesion on his scalp that slightly increase
in size & undergos central necrosis & ulceration.
2 weeks duration.
History of renal transplant.
No history of trauma
Mycophenolate mofetil.
Solitary ,tender, well defined, rounded, ulcer with central eschar, surrounded
by erythematous border & measure about 1 ×1 cm in diameter.
Vertex.
No LN++
No fever or systemic manifestation.
Skin
biopsy:

Alternariosis is a form of phaeohyphomycosis caused by
opportunistic molds of the genus Alternaria.

The genus Alternaria contains several species that cause
opportunistic human infections.

The most frequent clinical manifestations are:
Cutaneous and subcutaneous infections (74.3%).
Oculomycosis (9.5%).
Rhinosinusitis (8.1%).
Onychomycosis.
 Cutaneous
alternariosis is a deep mycotic
infection of the skin that has mostly been
described in immunocompromised hosts and
occasionally in healthy individuals.

Alternaria, are dematiaceous fungi, that characterized by
the deposition of melanin in their cell wall. Melanin is
thought to offer protection from environmental stress ( such
as radiation, temperature, and hydrolytic enzymes), and to
enhance the virulence and pathogenicity of the fungi.

The organism lives in soil, as saprophytes and parasites of
various plants.

Alternaria alternata

Alternaria gaisena

Alternaria senecionis

Alternaria arborescens

Alternaria helianthn

Alternaria solani

Alternaria arbusti

Alternaria helianthicola

Alternaria smyrnii

Alternaria blumeae

Alternaria infectoria

Alternaria tenuissima

Alternaria brassicae

Alternaria japonica

Alternaria triticina

Alternaria brassicicola

Alternaria leucanthemi

Alternaria zinniae

Alternaria brunsii

Alternaria limicola

Alternaria
carotiincultae

Alternaria linicola

Alternaria molesta

Alternaria padwickii

Alternaria panaxa

Alternaria petroselini

Alternaria radicina

Alternaria raphani

Alternaria saponariae

Alternaria selini

Alternaria carthami

Alternaria cinerariae

Alternaria citri

Alternaria conjuncta

Alternaria dauci

Alternaria dianthi

Alternaria dianthicola

Alternaria euphorbiicola
 Only
six species are described as human
pathogens: Alternaria
alternata, A
chlamydospora, A dianthicola, A infectoria,
A tenuissima, and A longipes.
 The
most commonly isolated species in
cutaneous alternariosis is A. alternata.
Also, A. infectoria has been found to
cause cutaneous lesions in few cases.
 The
infections are not contagious.

A main predisposing factor of alternariosis is immunsuppression,
which may be endogenous or therapeutically induced.

The most important risk factors for cutaneous and subcutaneous
infections are solid organ transplantation and Cushing's syndrome.
Three forms of alternariosis can be distinguished:

1. Exogenous, superficial form;

2. Exogenous, unilocular form of traumatic origin;

3. Endogenous, multilocular, disseminated form.

Clinical presented as painless seborrheic eczema like lesion
(localised erythema and desquamation of the skin).

The localization is mostly paranasal and on the cheeks.

Histological examination shows hyperkeratosis, parakeratosis, and
fungal elements in the epidermis. With progression of the disease,
microabcesses with fungal hyphae may be observed.

This form of infection follows a traumatic introduction of
the fungus into the skin (penetrating injuries).

This form is found in healthy persons. The skin lesion
appears as a livid-red plaque with superficial central
ulceration that may reach remarkable size.

The outbreak of mycosis can be as late as 10 years after
the initial inoculation and might be triggered by a
weakening of host defense mechanisms.

The skin lesions are found on bare parts of body, legs, and
arms. Usually, patients who work outdoors such as farmers,
gardeners, and car drivers are affected.

Histological examination of the skin biopsies of these patients
reveals
epidermal
acanthosis
and
parakeratosis.
A
subepidermal abscess contains neutrophils. The dermis shows
granulation tissue (granuloma) containing histiocytes, plasma
cells, and giant cells of foreign-body types.

Numerous round-shaped fungal cells and septate hyphae were
present both within giant cells and extracellularly.

The
most
common
form
often
seen
in
severely
immunocompromised patients.

This form most probably originates from metastatic invasion of
disseminated alternariosis.

Underlying conditions may be the following:
1. Hypercorticism caused by Cushing disease;
2. Neutropenia as a result of a malignant condition;
3. Organ transplantation and its treatment.

The entry of Alternaria species can be paranasal sinusitis,
pneumonia, or wound infection after surgery.

Skin manifestations appear with multiple erythematous and
partially
necrotic
papules
or
papulonodular
lesions
approximately 1 cm in diameter.

These lesions are most frequently painless, but they can be
quite painful.

The lesions are often found on the trunk, neck, and limbs.

The patient has good general condition ( afebrile, and have no
other signs of infection).

Histological examination of a skin biopsy reveals various
dermal granulomas, as well as an occasionally occurring central
abscess. Mixed infiltrates consisting of macrophages, plasma
cells, and neutrophils can be seen. No foreign body reaction is
observed.

Numerous round-shaped fungal cells and septate hyphae
were present both within granulomatous infiltrate.

Diagnosis of uncharacteristic inflammatory skin lesions in
patient under immunosuppressive therapy must include an
appropriate search for fungi.

Among the mycoses caused by opportunistic moulds,
alternariosis and fusariosis together with aspergillosis are
of particular importance.

A definitive diagnosis of alternariosis typically requires
both histologic and mycologic analyses (direct microscopy
& culture) of a biopsy sample.

Cutaneous alternariosis has been classified into two types: an
epidermal type and a dermal type.

In the epidermal type, the organism appears in the epidermis,
never invades the dermis, and hyphae are the predominant
elements.

In the dermal type, however, shows hyphae and yeast-like cells
invading the dermal layer.

Almost all reports of cutaneous alternariosis are dermal type.

Numerous round-shaped fungal cells and septate hyphae
were present both within granulomatous infiltrate.

These structures appeared:
Hyaline in H&E stained preparations.
Deep red with the PAS stain.
Black with a Grocott-Gomori methenamine silver stain.
Skin biopsy showing round-shaped fungal cells and septate hyphae
both within giant cells and extracellularly (periodic acid-Schiff stain)
Septate hyphae could be
methenamine-silver staining.
observed
with
Grocott-Gomori

The histological appearance of Alternaria may mimic that
of Aspergillus and they are not differentiated with
routinely used Gomori methenamine silver stain.

However, using the Fontana-Masson stain, Alternaria may
be distinguished from Aspergillus, because it contains
melanin and Aspergillus does not.

Direct microscopic examination after 15% to 30% KOH preparation of skin
samples shows numerous dark brown septate hyphae, partially branched
and sometimes few Alternaria conidia.

Skin samples are cultured on Sabouraud glucose agar with and without
cycloheximide at room temperature and 37C:

After 3 days of incubation, the culture of the skin samples forms whitebrown colonies.

No growth can be observed on cycloheximide-containing media.
Morphological identification is obtained on malt agar within 48 hours.

Very good growth and production of typical brown conidia in chains can
be found at 30C to 33C.
Potassium hydroxide wet
mount
of
the
biopsy
sample showing
an Alternaria conidium
with
characteristic
clublike
shape
and
transverse
(long
arrow)
longitudinal
arrow) septations.
and
(short
Microscopic appearance of the slide culture at room
temperature, Conidia in a chain with transverse and oblique
septa were observed.

Usually, cutaneous alternariosis is asymptomatic. Often, the
patients do not realize the skin lesions because they are painless
and non-pruritic.

The course of disease lasts many weeks or months. The prognosis is
good.

Spontaneous remissions of patients with dermatopathic form have
been published when the underlying condition improves and steroid
therapy can be stopped.

Fungal spread from primary cutaneous lesions has not been
described.
The treatment of cutaneous Alternaria infection is not standardized:

Reduction of immunosuppression when possible can be sufficient to treat
the lesions.

In patients with small and few lesions, local excision is recommended.

Treatment with cryotherapy has been successfully used for treatment of
multiple lesions of cutaneous alternariosis.

When complete excision or reduction of immunosuppression is not possible,
oral antifungal (ketoconazole, itraconazole, fluconazole or terbinafine)
are possible alternative treatments. (However, optimal antifungal dosages
and duration of therapy have not been standardized).

Itraconazole is suggested to be the drug of choice (in dosages ranging
from 100 to 600 mg/day).

Liposomal amphotericin B has also been successful in more advanced
cases.
Erythematous lesion on the back of the right hand.
The biopsy showed pseudoepithelimatous hyperplasia and dermal
infiltration of inflammatory cells. No fungal elements (Hematoxylin
and eosin staining).
Septate hyphae could be
methenamine-silver staining.
observed
with
Grocott-Gomori
A large, lichenified lesion with central necrotic eschar on the right
leg of a 17-year-old male patient 8 weeks after a penetrating
injury.
Potassium hydroxide wet
mount
of
the
biopsy
sample showing
an Alternaria conidium
with
characteristic
clublike
shape
and
transverse
(long
arrow)
longitudinal
arrow) septations.
and
(short
A -33-year-old man was diagnosed with chronic myelogenous leukaemia. He underwent an allogeneic BMT from
an unrelated donor. Three months later, a slightly itchy erythematous papule appeared on his left leg. During the
following days, 2 similar lesions developed on his left thigh and right arm. lesions increased a little in size and the
centre of the lesions became necrotic and ulcerated.
Microscopic appearance of the slide culture at room
temperature, Conidia in a chain with transverse and oblique
septa were observed.
A -58- y old male undergone a
renal transplantation since 15
months and immunosuppression
had
been
tacrolimus,
mofetil
&
maintained
with
mycophenolate
prednisone
since
then.
Multiple Painless reddish-brown
papules and vegetating masses
with smooth surfaces over both
legs extending to the ankles.
No
history
of
trauma
or
inoculation.
2006 Acta Dermato-Venereologica
Skin biopsy showing round-shaped fungal cells and septate hyphae
both within giant cells and extracellularly (periodic acid-Schiff stain)
2008 Acta Dermato-Venereologica.
A 68-year-old
renal transplant recipient
with an unspecific painless and erythematous nodule
on the lateral distal dorsal side of his right foot, which had developed within the last 2–3 months and
had reached a diameter of approximately 3 cm. The patient did not recall any preceding injury or
trauma at this site. He was under
continuous immunosuppressive therapy with
tacrolimus (4 mg daily), mycophenolate mofetil (1000 mg daily) and
prednisone (5 mg daily).
In the centre there are conspicuous large and thick-walled spherical
periodic acid-Schiff-positive fungal elements. Some are surrounded by
clear spaces