Palmar and plantar erythema: An initial presentation of undifferentiated connective tissue disease

Introduction

Undifferentiated connective tissue disease (UCTD) is a clinical entity with serologic and clinical manifestations of systemic autoimmune disease; however, it does not fulfill any criteria of defined connective tissue diseases (eg, lupus, mixed connective tissue disease, Sjögren syndrome, scleroderma, etc).¹ It can appear to have a mild clinical course and is marked by the absence of severe organ damage or involvement.^1,2 Pregnancy represents a possible trigger for the development of a connective tissue disorder; however, the influence of pregnancy on disease course is not well understood. We present the case of a pregnant woman with UCTD with an unusual cutaneous presentation.

Case report

A 29-year-old pregnant woman presented at a telemedicine dermatology visit with nonpruritic, blanching palmar, and plantar erythema on the left hand and foot (Fig 1). She was 17 weeks pregnant at the time of presentation and reported that eruption began at week 10 of gestation. Associated symptoms include intermittent tenderness and burning at the distal end of the fingertips. The patient’s dermatologic history was notable for atopic dermatitis, which was in remission. Medical history was significant for uterine leiomyomas, and medications included daily prenatal vitamins. She denied any other rashes, arthralgia, oral lesions, or cardiopulmonary symptoms. Differential diagnoses during dermatologic examination included acquired palmar erythema, Raynaud syndrome, eccrine hidradenitis, and erythema multiforme.

Fig 1.

Blanching palmar and plantar erythema on the palm of the left hand and sole of the left foot.

The histopathology of two 2-mm punch biopsy samples taken from the superior and inferior aspects of the left palm, demonstrated focal interface changes, in which lymphocytes approximated the dermoepidermal junction and are associated with vacuolar alteration. A superficial and deep perivascular as well as perieccrine lymphocytic infiltrate was observed in the dermis and dermal/subcutaneous junction. Both specimens showed associated mucinous ground substance (Fig 2). The periodic acid-Schiff stain did not reveal basement membrane thickening. Treponema pallidum staining was negative for spirochetes. The overall features of these biopsy results were most indicative of a connective tissue disorder.

Fig 2.

Representative histopathology of 2 biopsy samples from the superior aspect of the left palm. There is mucinous ground substance (blue arrowheads) in the dermis that extends into the dermal/subcutaneous junction. A, Staining demonstrates superficial, deep perivascular (yellow arrowheads) and peri-eccrine lymphocytic (red arrowheads) infiltrate. B, Focal interface with vacuolar changes (black arrow) at the dermoepidermal junction. (A and B, Hematoxylin-eosin stain; original magnification: A, ×1; B, ×3).

Laboratory assessment was completed to rule out connective tissue disease. Laboratory values were positive for antinuclear antibodies (1:2560), which was in a speckled pattern. Anti-Ro(SS-A) and anti-La(SS-B) antibody was elevated at 2.0 and 7.7, respectively. The remainder of an extensive autoimmune workup was unrevealing. Considering her pregnancy, an urgent consult to rheumatology was made.

She initially received a diagnosis of UCTD given a positive antinuclear antibody and inadequate additive criteria. At an initial rheumatologic assessment at week 19 of gestation, she started hydroxychloroquine 200 mg twice daily. She also completed periodic fetal echo monitoring until week 26 of gestation, which was unrevealing. At week 25 of gestation, follow-up with rheumatology demonstrated considerable improvement in the palmar and plantar erythema. Laboratory tests completed during this visit revealed nephrotic range proteinuria (urine protein/creatinine ratio, 7.4g). Therefore, postpartum renal biopsy was scheduled. One month after delivering a healthy, full-term, normal birth weight baby, the palmar and plantar erythema had completely resolved. At 3 months postpartum, she presented with dyspnea and received a diagnosis of bilateral pleural effusion, which was likely in the setting of nephrotic syndrome. Days later, renal biopsy demonstrated stage I-II diffuse membranous glomerulonephritis. With a nephrotic picture and high titer of antinuclear antibody–speckled pattern, this raised the possibility of glomerulonephritis related to an underlying, unspecified autoimmune disease process. Therefore, her 3-month postpartum course met the 2019 European League Against Rheumatism /American College of Rheumatology classification criteria for lupus (Table I).³ Consequently, she started a prednisone taper 60 mg per day, mycophenolate mofetil 1000 mg twice per day, and losartan 25 mg daily, while continuing hydroxychloroquine 200 mg twice per day. Roughly 1 year after renal biopsy, the patient experienced complete remission from nephrotic syndrome and had no proteinuria on quantification. She did not present with any new cutaneous or systemic complaints.

Table I.

Application of 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus to this case³

Entry criterion	Weight	Present (yes/no)
Antinuclear antibodies at a titer of ≥1:80 on HEp-2 cells or an equivalent positive test (ever)	If absent, do not classify as SLE.	Yes
	If present, apply additive criteria
Additive criteria
Constitutional		No
Fever	2
Hematologic		No
Leukopenia	3
Thrombocytopenia	4
Autoimmune hemolysis	4
Mucocutaneous		No
Nonscarring alopecia	2
Oral ulcers	2
Subacute cutaneous OR discoid lupus	4
Acute cutaneous lupus	6
Serosal		Yes (pleural effusion at 3 mo postpartum)
Pleural or pericardial effusion	5†
Acute pericarditis	6
Musculoskeletal		No
Joint involvement	6
Renal		Yes (proteinuria and stage I-II diffuse membranous glomerulonephritis on renal biopsy)
Proteinuria > 0.5g/24h	4
Renal biopsy class II or V lupus nephritis	8†
Renal biopsy class III or IV lupus nephritis	10
Immunologic		No
Antiphospholipid antibodies	2
Complement proteins (Low C3 OR Low C4)	3
Complement proteins (Low C3 AND Low C4)	4
SLE-specific antibodies	6
Total Score	13∗

SLE, Systematic lupus erythematosus.

^∗Classify as SLE with a score of ≥10 if entry criterion is fulfilled.

^†Within each domain, only the highest weighted criterion is counted toward the total score.

Discussion

This case highlights palmar and plantar erythema as a possible cutaneous manifestation of undifferentiated connective tissue disorder. Acquired palmar erythema was high on the differential list as it may present with widespread red and violaceous patches on the palms and fingers. Presentation is typically symmetric, asymptomatic, and involves thenar and hypothenar eminences. Our patient had some differences in typical presentation as feet are usually spared in acquired palmar erythema. Also, the patient’s lesions were patchy and did not fully involve the thenar and hypothenar eminences. The lesions were also asymmetrically distributed, and present only on the left hand and foot. On histopathologic assessment, acquired palmar erythema was revealed as dilated vessels in the dermis without any histologic signs of inflammation.^4,5 This patient’s histopathologic findings demonstrated focal interface changes and perieccrine lymphocytic infiltrate, confirming that acquired palmar erythema was not the appropriate diagnosis.

Although UCTD and systemic lupus erythematosus (SLE) are separate clinical entities, disease manifestations can be viewed along a continuum. Some cutaneous manifestations, particularly photosensitivity, are common in UCTD, whereas malar rash, discoid rash, or chronic cutaneous lupus would support a diagnosis of SLE.⁶ Leukopenia and thrombocytopenia can be found in approximately half of the patients with UCTD. However, other manifestations of severe SLE, such as renal disease, hemolytic anemia, and neurologic involvement, are unusual in UCTD.⁶ As seen in this patient, UCTD may progress to SLE, which demonstrates the need for early diagnosis and management to reduce long-term complications.⁶

Although UCTD is the most common rheumatic disorder diagnosed in pregnant women,² data on disease course and maternal-fetal outcomes are limited. One uncontrolled study of 20 pregnant patients with UCTD demonstrated that pregnancy may be a trigger for the development of a defined connective tissue disorder.⁷ Another study followed a cohort of 41 patients with newly diagnosed UCTD and a control group of healthy pregnant women.⁸ Compared with the control group, pregnant patients with UCTD were at increased risk of impaired intrauterine growth, prematurity, and delivered small-for-gestational-age infants.⁸ This supports the need to identify UCTD before or during early pregnancy. Women with UCTD should be tested for antiphospholipid autoantibodies and anti-Ro(SS-A) antibodies when planning pregnancy.⁶

Identifying the need for further investigation after unclear dermatologic presentation allowed this patient to have earlier multidisciplinary treatment and management. This patient’s elevated anti-Ro(SS-A) and anti-La(SS-B) antibodies also warranted further assessment due to the risk of neonatal lupus and congenital heart block. We present this case to increase awareness of rare cutaneous manifestations of UCTD.

Conflicts of interest

None disclosed.