Am J Clin Dermatol (2017) 18:333–341
DOI 10.1007/s40257-017-0256-2
THERAPY IN PRACTICE
Review and Management of Acneiform Eruptions in Patients
with Immune Disorders
Priyanka Vedak1 • Jessica St John1 • Daniela Kroshinsky1
Published online: 28 February 2017
Ó Springer International Publishing Switzerland 2017
Abstract Immune disorders are associated with acne or
acneiform lesions secondary to the occurrence of acne
vulgaris or acneiform eruptions arising as a result of
immunosuppressive medication or infection. In this review,
we aim to provide an overview of acne and acneiform
eruptions that can arise in the immunosuppressed host. Tips
for differentiating between various acneiform entities are
discussed, as well as a brief overview of treatment
considerations.
Key Points
The distinction between acne vulgaris in an
immunocompromised patient and an acneiform
eruption due to infection or medication is critical to
effective treatment.
The pathogenesis of many acneiform eruptions
remains unclear, with some immunomodulating
medications linked to both the causation of acne and
use as acne therapy.
Most traditional acne medications do not bear any
specific drug–drug interactions.
& Daniela Kroshinsky
dkroshinsky@mgh.harvard.edu
1
Department of Dermatology, Massachusetts General
Hospital, Boston, MA, USA
1 Introduction
Immune disorders are associated with a number of acnei-
form disorders secondary to either immunosuppressive
medication use or infections to which patients are at
increased susceptibility, secondary to their immunosup-
pressed status. In this review, we examine some general
helpful tips that can aid clinicians in distinguishing the
difference between the occurrence of acne vulgaris and an
acneiform eruption and, subsequently, delve into the
specific clinical presentations associated with various
infections and medications (Table 1). We also examine
drug–drug interactions and consequent treatment
considerations.
2 Acneiform Lesions Versus Acne Vulgaris:
Making the Clinical Distinction
For successful treatment, it is important to distinguish
between (1) acne vulgaris occurring in an immunosup-
pressed individual, and (2) an acneiform eruption occurring
in an immunosuppressed patient secondary to medication
use or infection. Clinical characteristics that can help guide
this distinction trace back to differences in the etiology of
these two conditions. In acne vulgaris, faulty keratinization
in the infundibula, ductal hypercornification, and increased
sebum production lead to the formation of comedones, with
secondary inflammation of these lesions resulting in the
formation of additional lesion morphologies, including
papules and pustules [1]. Lesions consequently tend to
localize in areas of increased sebum production, such as the
face, chest, and back. Meanwhile, in acneiform eruptions,
comedones are noted to be a secondary lesion that occurs in
response to a primary inflammatory lesion [2].
334 P. Vedak et al.

Table 1 Clinical presentations associated with various infections with recommended treatment options
Condition Clinical findings and Dermatopathologic findings Additional Treatment options
associations diagnostic clues

Pityrosporum Dome-shaped Inflammatory infiltrate consisting of Potassium Oral antifungals such as

folliculitis comedopapule with lymphocytes, histiocytes, and hydroxide itraconazole
central dell neutrophils with focal rupture of the scraping of Topical antifungals
May be pruritic follicular epithelium pustules reveals
Photodynamic therapy
Methenamine silver or periodic acid- spores
schiff stains can identify yeast Fungal culture
requires addition
of olive oil to
growth medium
Candida Can mimic tinea barbae Grocott’s methenamine silver stain or Tissue culture Oral antifungals such as
folliculitis periodic acid-schiff stain can identify fluconazole
yeast
Demodex Immunosuppression in Perifollicular and perivascular deep Tissue scrapings Permethrin cream,
folliculitis children inflammatory infiltrate and mite in show mites metronidazole cream,
Associated with immune follicular infundibula ivermectin, crotamiton,
reconstitution disease, sodium sulfacetamide and
immunosuppression in sulfur formulations
adults
Can be pruritic
Viral folliculitis Due to varicella zoster Varicella zoster virus: were necrotic Tzanck smear
virus, herpes simplex keratinocytes and multinucleated
virus, or molluscum epithelial-type giant cells with
contagiosum ground glass nuclei restricted to the
May not show vesicles follicular epithelium
May be spread by shaving Herpes simplex virus: ballooning
degeneration only around the
follicular epithelium with an
unaffected epidermis
Molluscum contagiosum: multiple
molluscum bodies in the epithelium
of the hair follicle
Eosinophilic Pruritic erythematous Inflammatory infiltrate of eosinophils Skin scrapings (may Including topical tacrolimus
folliculitis papulopustules that tend and lymphocytes around the hair show Demodex and NBUVB for HIV-
to spread centrifugally follicles and sebaceous glands spp.) associated cases
Can be associated with Topical corticosteroids,
peripheral eosinophilia NBUVB, infliximab for non-
May be associated with HIV immunosuppression-
HIV or hematologic related cases
malignancies
Trichodysplasia Follicular papules with Dilated hair follicles and proliferation Reducing immunosuppression
spinulosa extruding keratotic of inner root sheaths with enlarged in cases of organ
spicules usually located trichohyaline granules transplantation
on the face and ears Topical cidofovir and oral
Non-scarring alopecia valganciclovir
affecting the eyelashes May self-resolve with
and eyebrows resolution of
Associated with immunosuppression
immunosuppressive
therapy and hematologic
malignancies
Gram-negative Papulopustules and deep- NA Bacterial culture of Isotretinoin
folliculitis seated nodules anterior nares and
Associated with prolonged pustules
antibiotic use
Management of Acne in Patients with Immune Disorders
Table 1 continued
Condition Clinical findings and
associations
Topical and Monomorphic follicular
systemic papules with dull red
corticosteroids coloration with rare
pustules and few
comedones
Can be infected with
Pityrosporum ovale
EGFR inhibitors Pruritic acneiform
eruption on face and
trunk 1–3 weeks after
EGFR inhibitor initiation
Can be associated with a
secondary
Staphylococcus aureus
infection
Acneiform eruption can be
indicative of improved
tumoral response to
therapy
BRAF kinase Non-seborrheic
inhibitor distribution
Comedones
Associated with keratosis
pilaris,
keratoacanthomas,
squamous cell
carcinomas
Multikinase Papules and pustules on
inhibitor the face and upper trunk
(sorafenib)
MEK inhibitors Most frequent side effect
(trametinib) is acneiform eruption
HER2/neu Acneiform eruption with
inhibitor lesions larger than that
(trastuzumab) seen with EGFR
inhibitors
No clear association
between acneiform
eruption and tumoral
response
Cyclosporine Acne conglobata
Acne keloidalis nuchae
Associated with
hypertrichosis,
sebaceous hyperplasia,
and pilar keratosis
Sirolimus Inflammatory lesions as
(rapamycin) well as painful, nodular,
edematous lesions
335
Dermatopathologic findings Additional Treatment options
diagnostic clues
NA Potassium Cessation of corticosteroid use
hydroxide Traditional topical or systemic
scraping and treatments for acne vulgaris
fungal culture for
Topical or oral antifungals if
Pityrosporum
concomitant pityrosporum
ovale
folliculitis
Suppurative sterile neutrophilic None Oral tetracyclines (can be
folliculitis and perifolliculitis prophylactic)
Topical phytomenadione
(prophylactic)
Isotretinoin if severe
Topical tazarotene and
pimecrolimus have not been
effective
Rarely require cessation of
EGFR inhibitor therapy
Colloidal oatmeal lotion
Folliculitis with neutrophils noted None Same as EGFR inhibitor
within and around a hair follicle and acneiform eruptions
follicular rupture Do not use topical calcineurin
inhibitors
May require dose reduction
Colloidal oatmeal lotion
NA None Lesions are less severe when
trametinib is used in
combination with the BRAF
inhibitor dabrafenib
NA None Same as EGFR inhibitor
acneiform eruptions
NA None Stop cyclosporine
Non-specific folliculitis on biopsy Topical treatments for acne
vulgaris
Doxycycline, isotretinoin,
isoconazole
May require cessation of
sirolimus
336 P. Vedak et al.

Table 1 continued
Condition Clinical findings and Dermatopathologic findings Additional Treatment options
associations diagnostic clues

TNF antagonists More comedonal than NA None Discontinuation of TNF

inflammatory lesions antagonist in conjunction
with oral tetracyclines and
topical retinoids
Lenalidomide Inflammatory papules Suppurative and ruptured folliculitis Fungal culture may Desonide and doxycycline
topped with pustules demonstrate 100 mg/day for 3 months, as
Candida albicans well as a 2-week course of
fluconazole 50 mg/day
Intravesical Generalized pustular Follicular subcorneal pustules, Patch testing, Resolved within 7 days with
mitomycin C folliculitis spongiosis, inflammatory exocytosis potential role of no additional treatment
and a dense perifollicular dermal allergic contact
inflammatory infiltrate dermatitis
EGFR epidermal growth factor receptor, HER2 human epidermal growth factor receptor 2, MEK mitogen-activated protein/extracellular signal-
regulated kinase, NA not available, NBUVB narrow-band ultraviolet B, TNF tumor necrosis factor

Consequently, lesions demonstrate more widespread
involvement outside the usual sebaceous distribution,
including the forearms and buttocks. Clinical history may
also reveal a close relationship with drug exposure when
associated with medication use, including sudden onset,
monomorphic appearance, concomitant signs of drug tox-
icity, and lesion clearance after drug discontinuation [2, 3].
Pruritus may be seen in cases of certain infection-related
acneiform eruptions.
Adjunct diagnostic techniques such as microscopy,
culture, or biopsy may be helpful in making the distinction
between acne vulgaris and acneiform eruptions and will be
discussed with each disease entity when applicable. Drug–
drug interactions are discussed in Sect. 5.
3 Acneiform Eruptions Secondary to Infection
Pityrosporum folliculitis was first described in 1969 in
association with antibiotic use, but can additionally occur
in individuals with immunosuppression secondary to
widespread etiologies, including organ transplantation,
malignancy, diabetes, and HIV [4, 5]. Lesions occur due to
infection of the hair follicle by Malassezia spp., and may
be asymptomatic like acne vulgaris or pruritic in nature.
They have been described as a dome-shaped comedopapule
with a central ‘dell’ at the site of the hair follicle [6].
Diagnosis can be aided with potassium hydroxide micro-
scopy of scrapings acquired from monomorphic pustules,
revealing numerous spores and yeast. As Malassezia spp.
grows only within a medium rich in C12, C13, and C14 fatty
acids, growth in fungal culture is complicated, requiring
the addition of olive oil to the medium, and is rarely
required for diagnosis [4]. Tissue biopsy, also rarely
required for diagnosis, demonstrates an inflammatory
infiltrate consisting of lymphocytes, histiocytes, and
neutrophils with focal rupture of the follicular epithelium.
Yeast cells can be identified with methenamine silver- and
period acid-schiff-stained sections [6]. While topical
medications have demonstrated efficacy in immunocom-
petent and immunocompromised individuals, oral antifun-
gal treatment is often required in immunocompromised
individuals [5, 7, 8]. Neutrophil recovery may also be
required in hosts that have undergone bone marrow trans-
plantation [8]. While oral itraconazole has shown signifi-
cant improvement over placebo, use of oral ketoconazole is
now discouraged due to concerns regarding hepatotoxicity,
adrenal insufficiency, and drug interactions [9, 10]. Given
the risk of gastrointestinal discomfort, hepatotoxicity, and
the risk of drug interactions with oral antifungal treatment,
the use of photodynamic therapy has been investigated and
early data show limited but positive results [11].
Candidal folliculitis has been reported as a mimicker of
tinea barbae, termed folliculitis barbae candidomycetica
[12, 13]. It is unknown whether candida is the primary
source of infection or if it is secondary to an underlying
bacterial infection. It has also been seen in the setting of
candidemia in heroin users [14]. Predisposing factors
include underlying immunosuppression or prior treatment
with antibiotics or topical corticosteroids [15]. Candida
was isolated in suspected cases on mycologic culture, and
skin biopsy was often additionally performed, showing
yeast cells with either Grocott’s methenamine silver stain
or periodic acid-Schiff stain [13, 15]. Treatment involves
the use of oral antifungals such as fluconazole [12, 13, 15].
Demodex folliculitis occurs secondary to the commensal
follicle mites Demodex folliculorum and Demodex brevis,
which are frequently present in adults but rarely found in
children. In adults, demodex folliculitis may be seen as a
manifestation of immune reconstitution disease or as a
pustular eruption in tumor-stage mycosis fungoides
undergoing total skin electron beam therapy [16, 17], and it
Management of Acne in Patients with Immune Disorders
may mimic acute graft-versus-host disease [18]. Demodi-
cidosis in children occurs in the setting of immunosup-
pression, such as acute lymphoblastic leukemia [19].
Clinical findings include an acneiform eruption on the face
with periorificial accentuation, which may be pruritic.
Mites can be seen on skin scrapings or in the follicular
infundibula on biopsy, which additionally demonstrates a
perifollicular and perivascular deep inflammatory infiltrate
[20]. Treatment options include permethrin cream,
metronidazole cream, ivermectin, crotamiton, sodium sul-
facetamide and sulfur formulations [16, 19, 21].
Viral folliculitis can be seen in settings of immuno-
suppression and can be secondary to varicella zoster virus,
herpes simplex virus, or molluscum contagiosum, and
should be considered in the differential diagnosis when
acneiform lesions prove resistant to antibacterial or anti-
fungal therapy. In varicella zoster folliculitis, clinical sus-
picion must be high as immunocompromised hosts may
lack characteristic vesicles or pustules on examination
[22, 23]. Skin biopsy may not demonstrate many of the
typical features of herpes zoster infection and repeat
biopsies or deeper biopsy sections may need to be exam-
ined. In one case, necrotic keratinocytes and multinucle-
ated epithelial-type giant cells with ground glass nuclei
were restricted to the follicular epithelium noted only after
examination of deeper sections, allowing for the diagnosis
of varicella zoster folliculitis. Treatment involves a course
of oral valganciclovir [22]. Herpes simplex folliculitis can
present as vesiculopustular eruptions in the beard area or as
an acneiform truncal eruption with follicular vesicles
[23, 24]. Pathology can be challenging, demonstrating
ballooning degeneration only around the follicular epithe-
lium with an unaffected epidermis. Oral aciclovir can be
used for treatment [23, 24]. Molluscum folliculitis can
present as an asymptomatic eruption with non-umbilicated
skin-colored papules [23]. It has been described in the
beard area and on the legs, with shaving being implicated
as a source of spread [23, 25, 26]. Biopsy shows multiple
molluscum bodies in the epithelium of the hair follicle.
Curretage or cryotherapy can be used for treatment
[24, 26].
Eosinophilic folliculitis (EF) is a sterile inflammatory
dermatosis of unknown etiology characterized by pruritic
erythematous papulopustules that tend to spread centrifu-
gally. Two similar variants of EF have been described, one
associated with HIV infection and another in immuno-
compromised patients without HIV. The latter group
includes a number of patients with hematologic malig-
nancies who underwent stem cell transplantation (bone
marrow and peripheral blood) and those with hematologic
malignancies who did not undergo transplantation [27].
Additionally, a few case reports have described cases of
medication-associated EF, including EF induced by
337
chemotherapy [28]. Peripheral blood eosinophilia can be
seen. Biopsy is often required for diagnosis and demon-
strates an inflammatory infiltrate of eosinophils and lym-
phocytes around the hair follicles and sebaceous glands. No
treatment ensures cure of EF and various treatment options
have been proposed, including topical tacrolimus and
narrow-band ultraviolet B (NBUVB) for HIV-associated
EF, and topical corticosteroids and NBUVB for non-HIV
immunosuppression-related EF [29]. One case series of
therapy-resistant EF detected the presence of Demodex spp.
mites on skin scrapings and biopsy specimens from all
patients, and noted lesion improvement in all patients with
topical permethrin use [30]. Additionally, one case report
described improvement in a case of non-HIV-related EF
with use of the tumor necrosis factor (TNF) inhibitor
infliximab [31].
Trichodysplasia spinulosa (TS) is a rare disorder
reported in patients undergoing immunosuppressive ther-
apy and patients with hematologic malignancies. While it
is highly associated with TS-associated polyomavirus, the
exact pathogenesis remains unclear. Characteristic lesions
consist of follicular papules with extruding keratotic spi-
cules, usually located on the face and ears, and are asso-
ciated with non-scarring alopecia affecting the eyelashes
and eyebrows [32]. Biopsy reveals dilated hair follicles and
proliferation of inner root sheaths with enlarged tri-
chohyaline granules. Treatment options include reducing
immunosuppression in cases of organ transplantation and
the use of topical cidofovir and oral valganciclovir [33, 34].
Lesions may also resolve in their own with time, particu-
larly with the return of immune function [35].
Gram-negative folliculitis occurs in the setting of pro-
longed antibiotic use, particularly tetracyclines, when the
normal gram-positive flora of the skin is replaced with
gram-negative rods such as Escherichia coli, Pseudomonas
aeruginosa, Serratia marcescens, Klebsiella spp., and
Proteus mirabilis [36]. Both papulopustules and deep-
seated nodules can be seen. Bacterial culture of the anterior
nares and pustules can aid in diagnosis. Isotretinoin is the
treatment of choice as reduction of sebum reduces the
burden of gram-negative rods that rely on moisture for
proliferation [36].
4 Acneiform Eruptions Secondary to Medications
Topical and systemic corticosteroid (oral, intravenous, or
inhaled) use can induce an acneiform eruption thought to
be secondary to degradation of the follicular epithelium,
resulting in extrusion of the follicular content [37, 38].
Monomorphic follicular papules with a dull red coloration
are noted with rare pustules and few comedones [39]. One
study found that 80% of patients with acneiform eruptions
338
while undergoing corticosteroid treatment had significant
numbers of Pityrosporum ovale in the lesional follicle [40];
thus, treatment of corticosteroid acne may require cessation
of corticosteroid use, the use of traditional topical and
systemic therapies for acne vulgaris, or topical/oral anti-
fungals. Systemic corticosteroids are used in conjunction
with isotretinoin in the treatment of acne fulminans [41].
Epidermal growth factor receptor (EGFR) is found on
epithelial tissue and is implicated in the pathogenesis of
numerous solid organ tumors, where activation of EGFR leads
enhances tumor growth and progression. EGFR inhibitors
include cetuximab and panitumumab, which are monoclonal
antibodies against EGFR, and gefitinib and erlotinib, which
are EGFR tyrosine kinase inhibitors [42]. A potentially pru-
ritic acneiform eruption has been described on the face and
trunk 1–3 weeks after initiation of treatment with these agents
in more than 50% of patients [42, 43]. EGFR is found on
keratinocytes and it has thus been hypothesized that treatment
with EGFR inhibitors promotes terminal maturation of ker-
atinocytes and follicles, resulting in follicular occlusion,
inflammation, and thinning of the stratum corneum [44].
Biopsy of lesions reveals a suppurative sterile neutrophilic
folliculitis and perifolliculitis. Secondary staphylococcus
aureus infection has also been reported, with one study noting
an incidence of [50% [45]. With regard to oral treatment,
clinical trials have suggested efficacy of oral tetracyclines,
including prophylactic administration for a minimum period
of 6 weeks [46, 47]; for high-grade or refractory eruptions,
isotretinoin has been used [48]. With regard to topical therapy,
unfortunately neither tazarotene nor pimecrolimus have
demonstrated efficacy, but colloidal oatmeal lotion has yiel-
ded promising results [49–51]. Prophylaxis with topical
phytomenadione (vitamin K) pretreatment at either 0.05% or
0.1% concentration has also been associated with decreased
severity of acneiform eruption [52]. Very rarely, the severity
of the reaction has resulted in cessation of EGFR inhibitors
and treatment in a specialized burn unit [42]. EGFR-related
acneiform eruptions appear to portend an improved tumoral
response to therapy [43].
Vemurafenib, a small-molecule BRAF kinase inhibitor
used in the treatment of metastatic or unresectable me-
lanoma, is associated with acneiform eruptions. Lesions
may involve a non-seborrheic distribution and may include
comedonal lesions. Given that vemurafenib is associated
with other lesions related to keratinocyte proliferation, such
as keratosis pilaris, keratoacanthomas, and squamous cell
carcinomas, this same mechanism is believed to underlie
the associated comedone formation [53]. Skin biopsy is
consistent with folliculitis, with neutrophils noted within
and around a hair follicle and follicular rupture [54]. Given
that RAF is downstream of EGFR signaling, treatment
algorithms parallel those for EGFR inhibitor-associated
acneiform eruptions. Notably, given the association with
P. Vedak et al.
keratoacanthomas and squamous cell carcinomas, the use
of topical calcineurin inhibitors is not advised in BRAF
kinase inhibitor-associated acneiform eruptions for fear of
further promoting skin cancer formation [55].
Acneiform eruptions are rarely seen with the multikinase
inhibitor sorafenib, with one case report describing the
development of papules and pustules on the face and upper
trunk [56]. Treatment options that have shown success include
sorafenib dose reduction or colloidal oatmeal lotion [51, 56].
In contrast, acneiform eruptions are the most frequent side
effect of the mitogen-activated protein/extracellular signal-
regulated kinase (MEK) inhibitor trametinib. The combina-
tion of the BRAF inhibitor dabrafenib and trametinib is shown
to have superior progression-free survival for melanoma
compared with dabrafenib alone. Acneiform lesions are still
described with this combination therapy but are noted to be
less severe than that seen with trametinib alone [57].
An acneiform eruption has also been reported with trastu-
zumab, a human epidermal growth factor receptor 2 (HER2)/
neu inhibitor used to treat HER2-positive breast cancer
[58, 59]. Papules and pustules were noted to be larger in size
than those seen in association with EGFR inhibitors, ranging
from 0.5 to 1 cm [58]. Similar to EGFR inhibitors, the pro-
posed mechanism of action involves keratinocyte differenti-
ation [58, 59]. Given the paucity of reports of acneiform
eruptions in the setting of HER2 inhibitors, the association
between this eruption and survival time remains unclear [59].
Cyclosporine is a calcineurin inhibitor that is used for
immunosuppression in a variety of dermatologic diseases, as
well as in organ transplantation. Cyclosporine and iso-
tretinoin have been used together to treat acne fulminans
[41], while acne conglobata and numerous reports of acne
keloidalis nuchae have been described with cyclosporine use
[60–62]. Cyclosporine is known to accumulate in the skin.
Given the lipophilic nature of the molecule and its elimina-
tion through the sebaceous glands, the etiology of these
eruptions is hypothesized to be related to modification of the
pilosebaceous unit in transit. Indeed, a number of other
dermatologic manifestations of cyclosporine use are related
to this adnexal structure, including hypertrichosis, sebaceous
hyperplasia, and pilar keratosis [61]. Treatment may require
the cessation of cyclosporine use [60].
Sirolimus (rapamycin) is an inhibitor of the mammalian
target of rapamycin (mTOR) that serves as an alternative to
calcineurin inhibitors in preventing renal transplant rejec-
tion. Development of acne has been noted in 15–45% of
transplant recipients receiving sirolimus therapy, with no
correlation has been noted between acne occurrence and
sirolimus dose or trough level [1]. Male predominance,
inflammatory lesions, and painful, nodular, edematous
lesions have been described, with biopsy revealing a non-
specific folliculitis [1, 63]. The pathophysiology of sir-
olimus-induced acne is hypothesized to be similar to that of
Management of Acne in Patients with Immune Disorders
EFGR inhibitor-induced acne as sirolimus is a direct
inhibitor of EGF action via the mTOR pathway. Treatment
options include the use of topical acne treatments, doxy-
cycline, isotretinoin, and isoconazole. In some cases, ces-
sation of sirolimus was required [1, 64].
Acneiform eruptions have been seen secondary to all
three TNF antagonists [65, 66]. Unlike other drug-induced
acneiform eruptions, more comedonal lesions than
inflammatory lesions have been described, suggesting that
the retention of sebum may play a role in pathogenesis
[65]. Treatment involves discontinuation of the TNF
antagonist in conjunction with oral tetracyclines and topi-
cal retinoids. Like TNF-induced psoriasis, TNF-induced
acne is a paradoxical reaction, given that there have been
reports of the use of TNF antagonists in the treatment of
acne [67]. Similar to TNF-induced psoriasis, a genetic
predisposition may also be a contributing factor [68].
An acneiform eruption of inflammatory papules topped
with pustules has also been reported with the use of
lenalidomide, which is used in the treatment of multiple
myeloma, myelodysplastic syndromes, and systemic amy-
loidosis, and has pathways involving TNF- and EGFR-
dependent intracellular signaling pathways. Skin biopsy
demonstrated suppurative and ruptured folliculitis, bacte-
rial swab was negative, and fungal culture demonstrated
Candida albicans. Improvement was seen after 3 months
of treatment with desonide and doxycycline 100 mg/day
and a 2-week course of fluconazole 50 mg/day. [69].
Finally, a generalized pustular folliculitis has been
reported with intravesical mitomycin C. Skin biopsy
showed follicular subcorneal pustules, spongiosis, inflam-
matory exocytosis, and a dense perifollicular deral
inflammatory infiltrate. Lesions resolved within 7 days
with no additional treatment. An allergic contact dermatitis
component was suspected after a similar pustular eruption
occurred after patch testing with mitomycin C [70].
5 Drug–Drug Interactions and Treatment
Considerations
While early investigations on the effect of vitamin A on
skin transplant rejection had raised concerns regarding the
safety of isotretinoin use in transplant patients, later studies
demonstrated a reduction in the natural killer T cells
involved in acute organ transplant rejection in isotretinoin-
treated patients. Furthermore, low-dose isotretinoin has
been used to help prevent the occurrence of skin cancers in
renal transplant patients [71].
Azole antifungals, including itraconazole, are frequently
used to treat acneiform eruptions and affect the CYP3A4
cytochrome, which is one of the six main cytochromes that
oxidize medications during drug metabolism. Systemic
339
azole antifungal inhibitors of CY3A4 can notably influence
the metabolism of warfarin and cyclosporine, necessitating
increased monitoring of these medications [72]. For
example, in a case series of pityrosporum folliculitis in
orthotopic heart transplant recipients treated with oral flu-
conazole, serial cyclosporine levels were obtained and
revealed elevated, decreased, and constant cyclosporine
levels [73]. Interestingly, this characteristic of azole med-
ications was previously manipulated to help attain cost
savings and reduce infection rates. A randomized con-
trolled trial examining the use of concomitant ketoconazole
and cyclosporine post-cardiac transplantation versus
cyclosporine alone found that the addition of ketoconazole
allowed a reduction in cyclosporine dosage that saved
US$5200 the first year and had lower rates of rejection and
infection [74]. However, the US FDA has recently advised
that oral ketoconazole is no longer indicated for the treat-
ment of fungal infections of the skin or nails due to con-
cerns for severe adverse effects and drug interactions [10].
Additional drug interactions must also be kept in mind.
Oral ivermectin can be used to treat candidal folliculitis;
however, as candida folliculitis can be seen in HIV-in-
fected hosts, caution is advised when using this medication
with protease inhibitors or non-nucleoside reverse tran-
scriptase inhibitors as they are all substrates of the drug
carrier P-glycoprotein and animal studies suggest severe
potential interactions [15].
Care should be taken in patients with impaired renal or
hepatic function, both with regard to immunosuppressive
medications and potential treatments for acneiform eruptions.
Valaciclovir, famciclovir, aciclovir, tetracycline, and flu-
conazole all undergo renal clearance, as well as azathioprine,
cyclosporine, and methotrexate [75]. Topical cidofovir,
potentially used in the treatment of TS, requires caution when
used in immunosuppressed individuals, particularly those
with pre-existing renal disease. Acute renal failure has been
reported in such settings [76]. Prednisone undergoes hepatic
metabolism and is a weak inducer of CYP3A4 [75].
Additionally, immunosuppressed individuals may also
be taking additional medications for the treatment of other
systemic infections, which themselves may bear a number
of drug interactions. For example, rifampin is a known
potent inducer or major cytochromes, while trimetho-
prim/sulfamethoxazole and ciprofloxacin inhibit CYP2C9
and CYP1A2, respectively [75].
6 Conclusions
The appearance of acneiform lesions in the immunosup-
pressed patient necessitates the consideration of a variety
of causes, including disease-related, medication-related,
and infection-related eruption. Given that a number of
340
medications such as cyclosporine and infliximab have been
implicated in the causation of acneiform eruptions, and
have also been utilized to treat acne, further investigations
into the pathophysiology of these dermatologic findings are
required.
Compliance with Ethical Standards
Conflicts of interest Drs Vedak, St John and Kroshinsky have no
conflicts of interest to declare.
Funding No funding was received for the preparation of this article.
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