Lupus Erythematosus Panniculitis: Clinical and Histopathological

Diagnostic Challenge

Vashty Amanda Hosfiar

, Agung M. Rheza

, Sondang P. Sirait

, Eyleny Meisyah Fitri

Rahadi Rihatmadja

, Endi Novianto

Department of Dermatology and Venereology Faculty of Medicine Universitas Indonesia/

Dr. Cipto Mangunkusumo National Central General Hospital Jakarta

Corresponding auhtor

Keywords: Histopathology, Lupus Erythematous, Morphea, Panniculitis

Abstract: Panniculitis is the inflammation of subcutaneous fatthat sometimesassociated with connective tissue

diseases.One of the well-described forms of connective tissue panniculitis is lupus erythematosus

panniculitis (LEP). We report a 35-year-old female patient with skin atrophic lesions on the lateral aspect of

the upper arms and cheeks for at least 8-year duration. The atrophic lesions were followed by recurrent

multiple small nodules on the right jaw and neck, on which excisional biopsy was performed.

Histopathologyexamination revealed lobular panniculitis consistent with LEP. However, slight hyalinosis

and thickened collagen bundles were also observed that deep morphea could not be ruled out. The patient

was treated with hydroxychloroquine 200 mg/day and methotrexate 7.5 mg a week, showing improvement

by decreased ANA titer. No new nodules and enlargement of atrophic areas were found after the one-month

course of therapy.

1 INTRODUCTION

Inflammation of the subcutaneous fatknown as

panniculitis can be seen in many disorders, including

connective tissue diseases. Panniculitis occurring in

connective tissue diseases are lupus erythematosus

panniculitis (LEP), panniculitis associated with

dermatomyositis, morphea, and scleroderma, which

were also known as connective tissue panniculitides

and associated with autoimmune phenomena.(Gupta

P et al., 2016; Braunstein I et al., 2012)

LEP, or also

known as Kaposi-Irgang disease, is a rare form of

chronic cutaneous lupus erythematosus

characterized by inflammatory lesions in the lower

dermis and subcutaneous tissue,(Costner et al., 2012;

Aronson IK et al 2012).The most important

differential diagnosis of LEP is deep morphea.

Morphea or localized scleroderma is a chronic

autoimmune disease characterized by sclerosis of the

skin.(Costner et al., 2012; Saxton-Daniels et al.,

2012).Diagnosing panniculitis is often difficult due

toinadequate clinical details, overlapping clinical

and histopathological features, inadequate biopsy

specimens, and evolving morphology of different

types of panniculitides at different

stages.

Panniculitis associated with connective tissue

diseases resolves with depressed atrophic scar

leading to cosmetic disfigurement and decrease in

quality of life. (Braunstein I et al., 2012;Hansen CB

et al., 2010). report a case of connective tissue

panniculitis featuring atrophic lesions on upper arms

and cheeks for at least 8-year duration. Despite

previous histopathology evaluation, it was not

correctly diagnosed that definitive treatment had

been delayed leading to permanent atrophy. This

case report aimed to raise the awareness of the

entity, the importance of skin biopsy for diagnosis,

and prompt treatment to improve quality of life.

2 CASE

A 35-year-old female presented with skin atrophy on

the lateral aspect of the upper arms for 12 years and

cheeks for eight years. The lesions started as bluish-

red bumpswithout pain or itch. Over six months,

lesions progressed to atrophic scar with healthy

skinappearance. She also had suffered from a similar

process on her cheeks for eight years, followed by

272

Hosﬁar, V., Rheza, A., Sirait, S., Fitri, E., Rihatmadja, R. and Novianto, E.

Lupus Erythematosus Panniculitis: Clinical and Histopathological Diagnostic Challenge.

DOI: 10.5220/0009986402720276

In Proceedings of the 2nd International Conference on Tropical Medicine and Infectious Disease (ICTROMI 2019), pages 272-276

ISBN: 978-989-758-469-5

multiple small nodules on the right jaw and neck.She

underwent surgical excision and was diagnosed with

tuberculosis lymphadenopathy by an internist. She

was treated with a fixed-dose combination of anti-

tuberculosis drugs for six months, and the nodules

were improved.Over the past ten months, multiple

recurrent nodules had developed on the right neck.

She underwent fine-needle aspiration biopsy,

resulted as a benign submandibular lesion, and she

was referred to oncology surgeon in our hospital. An

excisional biopsy was performed, histopathology

and immunohistochemistry examination confirmed a

reactive polyclonal lymphoproliferativeprocess

(lymphocytes positive for CD30, CD20, CD138,

CD4, CD8, and Ki67 20% of a nucleus).She was

consulted to the hemato-oncology division and

dermato-allergo-immunology division.No history of

skin trauma, fever, malaise, weight loss, stomatitis,

joints, pain, or hair loss was found. There was no

history of malignancy or similar symptoms in the

family.

Physical examinations revealedmultiple atrophic

lesions on the cheeks and lateral aspect of the upper

arms with the normal skin surface. There were

twoimmobile and painless lymph node enlargement

in the neck and submandibular region, 1x1x0,5 cm

in size. Chest x-ray examination result was within

normal limits. Ultrasonography of neck showed right

mandible isoechoic lesion and partially bilateral

multiple conglomerated right intraparticle lymph

nodes.Level II right neck lymphadenopathy was

found in CT scan of the neck with contrast.

Laboratory test results showed normal levels of

complete blood count, renal and liver function tests,

but a decrease in vitamin D 25-OH level (21ng/dl).

HIV screening assays, HBsAg, anti-HCV, C3,

C4levels, and anti-dsDNA test were

negative.ANA1/1000, coarse speckled pattern,

possible antibodies on hnRNP, U1RNP, Sm, RNA

Polymerase III. Ro-52 recombinant borderline and

SS-B positive in ANA profile.

In the dermato-allergo-immunology clinic, patients

were suspected of LEP, different from the earlier

histopathologic result. So, we asked for a

reevaluation of the biopsy specimens to

dermatopathology division. Histopathology reading

revealed epidermal atrophy, vacuolaralteration, and

flattening of rete ridges; perivascular and

periadnexal lymphohistiocytic infiltrates forming

lymphoid follicles; and lymphohistiocytic infiltrates

among fat lobules which showed partial necrosis

with corresponding Touton giant cells, and

lipophage, supporting a diagnosis of LEP. Ziehl-

Neelsen, Periodic Acid-Schiff (PAS), and Gram

staining did not demonstrate acid-fast bacilli,

thickened basement membrane, and bacteria

respectively. However, as there was suspicion for

morphea, another reading was done that found what

was considered as hyalinized and thickened collagen

bundles. The diagnosis of LEP with deep morphea

as a differential diagnosis was made.

After confirming a normal glucose-6-phosphate

dehydrogenase (G6PD) level and no ophthalmic

contraindication to an antimalarial drug, the patient

began treatment with hydroxychloroquine 200 mg a

day and topical sunscreens. Later atone month

follow uplesions were stable without new nodules,

andANA titer decreased to 1/320. Methotrexate was

given in initial dose 5 mg a week, escalated to 7.5

mg a week accompanied with folic acid 5 mg a week

orally in addition to hydroxychloroquine.During the

last threemonths,the atrophic lesions were stable, no

new nodules were found, and multiple nodules on

the right neck decreased in size.

Figure 1. AE. Multiple atrophic lesions with normal skin surface (arrow).

Lupus Erythematosus Panniculitis: Clinical and Histopathological Diagnostic Challenge

273

Figure 2. Histopathology with Hematoxylin-eosin (HE) staining A. HE,50x, perivascular and perifollicular

lymphohistiocytic infiltrates extending to the subcutis (arrow). B. HE, 100x, lymphoid follicles (arrow). C. HE, 400x,

lymphoid follicles (arrow). D. HE, 1000x, lymphohistiocytic infiltrates (yellow arrow) and fat lobules necrosis (green

arrow).

3 DISCUSSION

Panniculitisassociated with connective tissue disease

begins with active inflammation and develops into

atrophy, scar, and calcification.(Gupta P et al., 2016;

Braunstein I et al., 2012;Hansen CB et al., 2010)

Diagnosis of LEP and deep morphea as a differential

diagnosis were established based on clinical,

laboratory, and histological findings. LEP is

characterized by inflammatory of the lower dermis

and subcutaneous tissue, estimatedto comprise

13% of cutaneous LE cases. (Costner et al.,

2012;Aronson IK et al., 2012)

LEP lesions begin

with subcutaneous nodules without or with any

surface changes including erythema and discoid

lupus erythematosus (DLE) features. The most

common sites are on the lateral aspect of upper

arms, shoulders, face, scalp, hips, breasts, and

buttocks. The mean duration of the disease is

sixyears and resolves with depressed lipoatrophic

areas. (Aronson IK et al., 2012). Clinically, the

disease’s course and location in our patient matched

with those of LEP. Fifty percent of LEP patients

could develop systemic lupus erythematosus (SLE)

with mild manifestations. (Fett N et al.,

2011;Castrillon MA et al., 2017). On the other hand,

Deep morphea is a chronic autoimmune disease

characterized by skin sclerosis that involves the deep

dermis, subcutaneous tissue, fascia, and muscle.

Both diseases are more common in females aged

3060 years old and resolve with depressed atrophic

scar. (Costner et al., 2012; Saxton-Daniels et al.,

2012; (Fett N et al., 2011)

Serologic analysis for LEP are often normal, and

sometimes variable positive ANA titer demonstrated

ranging from 2795,4% of cases. Less frequently,

anti-ds-DNA antibodies are present. (Aronson IK et

al., 2012; Castrillon MA et al., 2017;Zhao YK et al.,

2016)

In our patient, the laboratory showed ANA

titer 1/1000. However, anti-dsDNA is not present.

Positive ANA could also be found in 3980%

morpheawith speckled pattern (81%) andtiter

>1/1280. (Saxton-Daniels et al., 2012;Teke MN et

al., 2017)

The gold standard of LEP diagnosis is the

histopathology examination result from a deep skin

biopsy of the lesional area.(Castrillon MA et al.,

2017;Bednarek A et al., 2015).The histopathological

finding of LEP shows mostly lobular or mixed

panniculitis with a variable lymphocytic infiltrate.

Meanwhile, panniculitis on deep morphea is

predominantly septal. (Gupta P et al., 2016;

Bednarek A et al., 2015)

In our patient, the

important findings included lymphoid follicles (that

lead to the previous diagnosis of lymphoproliferative

disorder), necrosis of fat lobules, and what was

thought later to be hyalinized and thickened collagen

bundles. With these overlapping clinical and

histopathological features, diagnosis in our case was

made with a degree of uncertainty. Lipoatrophic

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274

panniculitis is a diagnosis of exclusion that requires

evaluating for other causes of panniculitis. (Aronson

IK et al., 2012; Hansen CB et al., 2010). In our

patient, laboratory findings within normal limits and

staining for Ziehl-Neelsen, Periodic Acid-Schiff

(PAS), and Gram examination were used to

eliminate infection, all returned negative. The

differences between LEP and deep morphea are

depicted in Table 1.

As immunohistochemistry examination confirmed a

reactive polyclonal lymphoproliferative disease,

another important differential diagnosis is

subcutaneous panniculitis-like T-cell lymphoma

(SPTCL), a lymphoma whose origin is from mature

cytotoxic T cells.(Sugeeth et al., 2017;Lerma IL.,

2018;Arps DP et al., 2013).

As lymphocytes were

positive for CD3, CD4, CD8, and CD20 (B cells

marker) in our patient, SPTCL were excluded.

Antimalarial drugs such as hydroxychloroquine or

chloroquine are usually the first-line treatment for

LEP. Antimalarials interfere with inflammatory

cytokinesas well as TLRs, requiring at least three

months to show effectiveness. (Costner et al.,

2012;Aronson IK et al., 2012).

The patient has

treated with hydroxychloroquine 200 mg a day with

good response, shown by decreased ANA titer from

1/1000 to 1/320, no new nodules or enlargement of

atrophic lesion found after a month. Since

methotrexatewas recommended as a first-line

treatment for morphea with dermal and

subcutaneous involvement,

five

we also added

methotrexate to previous hydroxychloroquine

treatment.

Table 1.Summary of clinical features, laboratory findings, and histopathology in LEP and deep morphea. Bold words are

found in our patient

Characteristics LEP Deep morphea

Clinical features - Subcutaneous nodules without or with any

surface changes.

- Location: lateral aspect of upper arms,

shoulders, face, scalp, hips, breasts, and

buttocks.

- Resolve with atrophic scarring.

- Sclerotic plaque with hyperpigmented,

ill-defined, or mildly inflamed.

- The skin feels bound down to the

underlying fascia and muscle.

- Resolve with atrophy,

hyperpigmentation, or discoloration.

Laboratory

findings

- The serologic analysis is often normal.

- Positive ANA titer ranging from 2795,4%.

- Anti-ds-DNA antibodies are less frequently

present.

- Serologic analysis: peripheral

eosinophilia, hypergammaglobulinemia,

and raised ESR.

- Positive ANAcan be found.

- Other autoantibodies: Anti ds-DNA, anti-

histone, anti-Scl-70, and rheumatoid

factor.

Histopathology - Predominantly lobular panniculitis or mixed

panniculitis.

- Variable lymphocytic infiltrate, lymphoid

follicles, and hyaline fat necrosis.

- Other characteristics: DLE-like changes in

epidermis, dermo-epidermal changes,

mucin deposition, granuloma formation,

plasmacytic infiltration, and calcifications.

- Predominantly septal panniculitis.

- Lymphocyte and plasma cell infiltration

and collagen tissue thickening and

hyalinization in the subcutis.

- Occasionally, lymphoid follicles devoid

of germinal centers.

- Lipophagic granuloma also may be

present in the fat lobules.

4 CONCLUSION

Diagnostic of panniculitis poses achallenge due to

various factors. Many conditions that could cause

panniculitis to need to be excluded. Histopathology

examination from a deep skin biopsy is still

remained to be the gold standard. Clinical and

serologic characteristics should always be weighed

in for a final diagnosis.Particularly in LEP,early

diagnosis and appropriate therapy should be

considered to prevent disfigurement and progression

to systemic involvement.

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