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July 2023 Volume 7 Issue 4

COMPELLING COMMENTS

Patch-Type Granuloma Annulare with Clinical and Histological
Features of Morphea: A True Overlap?

Carlie Reeves, BA, MS1, Lauryn M Falcone, MD, PhD2, Colleen J Beatty, MD2, Viktoryia
Kazlouskaya, MD, PhD2, Joseph English III, MD2

1 University of Mississippi Medical Center, Jackson, MS
2 Department of Dermatology, University of Pittsburgh, Pittsburgh, PA

GA is a chronic granulomatous disorder that
usually presents as erythematous papules or
plaques in an annular arrangement1.
Histologically, GA is characterized by mucin
deposition, lymphohistiocytic infiltrate, and
degeneration of collagen2. Numerous inciting
factors for GA have been reported, including
viruses, arthropods, HIV, and Borrelia
infection1. GA often spontaneously resolves
and is mostly a cosmetic concern to patients.
However, some forms of GA are associated
with systemic disease, such as generalized
GA and diabetes mellitus (DM)3. Patch-type
GA is a distinct variant of this condition,
presenting with large asymptomatic annular
plaques4. This peculiar GA type is often
misdiagnosed with other dermatoses, more

commonly tinea, morphea, or mycosis
fungoides. Histopathologically, it also differs
from classical GA, closely resembling
inflammatory stages of morphea and
interstitial granulomatous dermatitis of
autoimmune disease, and interstitial drug
eruption4. Herein, we described a case of
patch-type GA with overlapping features of
morphea and discuss the existing literature of
the topic.

A 67-year-old woman with a past medical
history of essential hypertension, type 2
diabetes, and hypercholesterolemia was
evaluated in an outpatient dermatology clinic
for an asymptomatic, erythematous rash on
the trunk and legs that had been worsening

ABSTRACT

A 67-year-old woman was evaluated for a worsening asymptomatic rash located on her torso,
back, and legs. She denied any chills or fevers and reported feeling otherwise well. Clinically,
large brownish, slightly atrophic plaques were seen on the torso suggestive of either morphea
or a granulomatous condition. Histopathologic examination revealed an increase in interstitial
histiocytes infiltrating between altered collagen fibers, palisaded granulomas with increased
mucin, suggestive of granuloma annulare (GA), as well as dermal sclerosis, perineural
infiltrates with plasma cells and diminished CD34 counts, that are more typical for localized
scleroderma/morphea. Morphea and patch-type GA may be indistinguishable clinically and
share some histopathological features. This case demonstrates similarities between these
conditions and features of both conditions in the same patient.

INTRODUCTION

CASE REPORT

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Figure 1. (A): Clinical photograph of left breast exhibiting erythematous skin with sharp border (B): Clinical
photograph exhibiting erythematous, annular patches of various sizes, located mostly on the lateral back.
Some patches demonstrate central clearing (arrow) (C): Clinical photograph of erythematous, confluent
patches that cover the majority of the right side and axilla (D): Clinical photograph of the medial torso
featuring a large erythematous patch with sharp borders.

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Figure 2. (A): Marked sclerosis and thickened collagen bundles of the superficial and mid dermis zone
(zone A) with foci of interstitial granulomatous infiltrate (zone B) and zones of perineural inflammation
(zone C), Hematoxylin Eosin stain, x40. (B) Higher magnification of the interstitial granulomatous infiltrate
and homogenized collagen, Hematoxylin Eosin stain, x200. (C): Higher magnification of perineural infiltrate
with collections of plasma cells, Hematoxylin Eosin stain, x200. (D): Increased amount of interstitial mucin,
Alcian Blue stain, x100. (E): Loss of CD34 immunostain in the superficial dermis, CD34 immunostain, x100.

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over the previous 6 to 8 months (Figure 1).
The rash was characterized by large, non-
scaly, brownish patches with central
atrophy/clearing.

Laboratory evaluation was notable for low
vitamin D levels. Lyme disease antibodies
were negative.

Punch biopsies from the lower back and
abdomen revealed significant thickening of
the dermal fibers with homogenization in the
superficial dermis and thickened fat septae.
There was an interstitial infiltrate of spindled
histiocytes infiltrating between swollen
collagen fibers, and focally increased
interstitial mucin. Scattered rare eosinophils
were also noted as well as perineural plasma
rich cell infiltrate. In addition, there is
extensive sclerosis of the superficial and
middle dermis with diminished CD34 counts
(Figure 2). Periodic acid-Schiff (PAS) stain
was used to identify any fungal
microorganisms and basement membrane
changes, both of which were absent. The
patient was diagnosed with interstitial GA and
possible morphea overlap and started on
methotrexate 15 mg per week. The rash
showed significant improvement on
methotrexate after three months.

Patch-type GA is a poorly described entity.
The largest clinic-morphological study of
patch GA by Khanna et al demonstrates the
challenges in diagnosing this condition4.
Histopathologically, it was described to have
unique features including predominantly
interstitial infiltrate and presence of
eosinophils and plasma cells4. The authors
mention that these features were not
previously described in the previous reports
of patch-type GA and are usually considered
features of morphea. We, additionally, found

the presence of perineural infiltrates with
plasma cells previously described as features
of morphea5.

Interestingly, coexisting morphea and GA
was described in a few reports in the
literature. The first known case described a
62-year-old patient with linear morphea on
pretibial surfaces and GA on the medial
thigh6. Two more patients were reported in
1999: one patient had GA on the thigh and
morphea on the chest; the second patient
had morphea on the right breast and lateral
back and GA on the inner thigh and right
shoulder2. A third report from 2019 describes
a patient with morphea on the lower limbs
and GA on the abdomen and dorsum of the
feet7. Another interesting case report
described the development of morphea after
granulomatous fasciitis induced by Lyme8.

It has been suggested that the coexistence of
these conditions may be due to a common
etiological link such as autoimmunity or
previous injury6. Antinuclear antibodies
(ANA) may be increased in up to half of all
cases of morphea9. However, this is a non-
specific finding as even healthy individuals
can have a positive ANA. In our patient, ANA
was negative. Scleroderma and centromere
B antibodies, which are ANAs specific for
systemic sclerosis, were also within normal
limits10. In regard to previous injury, studies
have shown that repeated friction, as occurs
along the bra line and waistband area, may
play a role in morphea developing at those
susceptible sites11. Our patient had patches
along the underside of the breast which
frequently contacts the bra lining (Figure 1-
D). However, our patient also had more
diffuse involvement across her back and
chest in areas that would not be subject to
repetitive friction.

Our patient had several comorbidities that
may be risk factors for developing GA,

DISCUSSION

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including diabetes mellitus (DM) and
hyperlipidemia. A 2021 study investigated the
findings of 5,137 patients with GA.
Investigators reported that 21% of patients
with GA had DM compared to the 13% seen
in the control group. A larger percentage of
patients with GA had hyperlipidemia
compared to the control group (33% vs
28%)12. This study suggested that DM and
hyperlipidemia may predispose one to GA
through T-cell dysregulation. Other studies
have found T-helper 1 cells (Th1), T-helper 2
cells (Th2), and the Janus kinase-signal
transducer and activator of transcription
(JAK-STAT) pathway to be implicated in
dysregulation of GA13. Increased expression
of cytokines corresponding to the T-cell axes
were noted; this is particularly true for IL-4
mRNA (corresponding to the Th2 pathway),
which exhibited a 15,600-fold increase in GA
lesions versus control skin13.

An interesting finding shared by GA and
morphea is that both exhibit alterations in
collagen and CD34 loss2,14,6. It has been
proposed that the collagen degeneration
seen in GA is mediated by M1 macrophages,
a type of macrophage that initiates
inflammation15. Inflammation is then followed
by an M2 macrophage mediated response,
resulting in mucin deposition15. Collagen
degeneration can be analyzed by
immunohistochemical staining for CD34.
CD34 is a marker for vascular endothelial
progenitors16. Endothelial cell damage has
been proposed as an inciting factor in
developing morphea17. An important finding
in morphea is the loss of CD34 dermal
dendritic cells (DDCs)18. This CD34 loss is
also seen in GA18. Findings from an
investigation that analyzed 50 skin lesions
from patients with morphea suggest that a
phenotypic change of CD34+ DDCs to
smooth muscle actin positive (SMA)
myofibroblasts is responsible for the disease
extent and fibrosis in morphea19. Because

CD34 counts are decreased in both morphea
and GA, phenotypic changes of CD34+
DDCs could play a role in the overlapping
nature as seen in our patient. However, it is
rare for GA and morphea to occur in the same
patient and even more rare for the diseases
to occupy the same location. Thus, more
studies are needed to further discuss what
etiological link, if any, may connect these two
disorders.

To conclude, we report a case of patch-type
granuloma annulare with clinical and
histopathological features of morphea. This
case presents a challenging clinical and
pathologic differential diagnosis and raises
the possibility of an overlap of these two
conditions. Further studies are needed to
better elucidate what etiologic link, if any,
exists between these two entities.

Consent: All ethical standards have been
maintained. Patient gave consent to the production of
this manuscript.

Conflict of Interest Disclosures: None

Funding: None

Corresponding Author:
Carlie Reeves, BA, MS
University of Mississippi Medical Center
Jackson, MS
Email: creeves4@umc.edu

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CONCLUSION

mailto:creeves4@umc.edu

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