Table 1. Differential diagnosis of acute hand swelling.

COVID-19: coronavirus disease 2019; CR: current report; POTASH: post ambulatory swollen hands; Refs: references; RS3PE: remitting seronegative symmetrical synovitis with pitting edema; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2

Diagnosis	Comments	Refs
Allergic contact dermatitis	Painful and pruritic, progressive erythema and bilateral hand swelling of two days duration in a 45-year-old man. He began using a new antiseptic hand wash during the prior seven days. Patch testing confirmed that the contact allergen was the antiseptic chloroxylenol.	Dickson and Fischer, 2019 [4]
Compartment syndrome	There are several etiologies for compartment syndrome: bites (crotalid snake envenomation and arthropod assault from spiders and scorpion), bleeding (hypercoagulable state and vascular injury), burns (electric and thermal), constrictive cast or bandages with prolonged traction, high-pressure injection, infection (abscess and necrotizing fasciitis), infiltrated intravenous line or infusion, muscle overuse (exercise, seizure, and tetany), reperfusion injury, and trauma (crush injuries, direct muscular contusion, fractures, and prolonged limb compression. In addition to hand swelling, physical findings (which include the five Ps) are disproportionate pain, pallor, paralysis, paresthesia, and pulselessness. To preserve hand function and avoid tissue damage, early recognition is crucial and compartment release (utilizing emergency fasciotomy) may be necessary.	Oak and Abrams [5]
Deep venous thrombosis	A thrombus of a deep upper extremity vein can present with painful swelling of the arm and hand; warmth and erythema or discoloration are also present. It can be caused by damage to the blood vessel walls (such as from venous catheter placement), hypercoagulability, and/or stasis.	Studdiford and Stonehouse, 2009 [3]
Erythromelalgia	Primary or secondary erythromelalgia presents with recurrent episodes of bilateral and symmetrical, erythematous, warm, painful (such as burning) swollen hands and feet. Relief results from elevation of and cold exposure to the extremity. Low-dose daily aspirin can provide resolution of primary erythromelalgia. Secondary erythromelalgia can be associated with multiple conditions including myeloproliferative disorders.	Hart, 1996 [6]
Exercise-induced urticaria	Exercise-induced urticaria is part of a range of disorders which includes exercise-induced anaphylaxis and food-dependent exercise-induced anaphylaxis. Hand swelling (presenting as hives) may be a component of exercise-induced urticaria; however, lesions are usually widespread. In addition to urticaria and collapse during or after exercise, other symptoms include angioedema, flushing, gastrointestinal symptoms, hypotension, pruritus, and respiratory symptoms.	Studdiford and Stonehouse, 2009 [3]
Infection	Cellulitis secondary to Staphylococcus aureus or Streptococcus pyogenes (erysipelas) can result in erythematous swelling of the hand.	Dickson and Fischer, 2019 [4]
Irritant contact dermatitis	Excessive hand washing can result in xerosis, fissures, and tender, potentially swollen, hands; the thinner skin of the dorsal hands is most susceptible than the thicker palmar skin.	Dickson and Fischer, 2019 [4]
Medications	Medication-induced edema may occur immediately or up to several weeks after starting a drug. It may be generalized or restricted to specific areas such as swollen lower extremities or hand swelling. Usually, it resolved within days after stopping the causative agent. Medications commonly associated with edema include antidepressants (monoamine oxidase inhibitors, tricyclics, and trazodone), antihypertensives (beta-adrenergic blockers, calcium channel blockers, clonidine, hydralazine, methyldopa, and minoxidil), anti-Parkinsonism drugs (pramipexole), antivirals (acyclovir), chemotherapeutics (cyclosphosphamide, cytosine arabinoside, and mithramycin), cytokines (granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interferon alpha, and interleukin-2), hormones (androgens, corticosteroids, estrogen, progesterone, and testosterone), hypoglycemic agents (thiazolidinediones: pioglitazone and rosiglitazone), immunosuppressants (cyclosporine), and nonsteroidal anti-inflammatory drugs (celecoxib, ibuprofen, and naproxen).	Studdiford and Stonehouse, 2009 [3]
Nocturnal hand swelling	In healthy individuals without active or prior hand pathology, overnight (which was defined to be from 8 PM to 8 AM), there was an overall 4.5 percent increase in average hand volume. The consistent physiological nocturnal hand swelling was attributed to fluid retention; the hand volume returned to baseline during the next day (from 8 AM to 8 PM).	Warrender et al., 2019 [7]
POTASH	Post ambulatory refers to the onset of the asymptomatic hand swelling occurring after the initiation of--yet while still participating in--either hiking, running, or walking. Both the dorsum and palm of the hand become swollen; there is a positive fist sign: the individual cannot clench their fingers to make a fist. The hand swelling resolves spontaneously, usually within one to two hours, after the ambulatory activity has been discontinued.	Ravaglia et al., 2011 [1], DesMarais, 2021 [2], CR
Post COVID-19 puffy hands	Two women (28-years-old and 33-years-old) presented with non-resolving, isolated, bilateral, erythematous, tender to palpation, non-pitting edema of the hands and fingers with fissures over the interphalangeal joints. Six and eight weeks prior to the onset of their hand symptoms, respectively, each had a positive result for SARS-CoV-2 with real-time polymerase chain reaction testing of a nasopharyngeal swab sample. Hand swelling occurred after all acute COVID-19 viral symptoms had resolved and repeat testing for the virus was negative. The investigators proposed a capillary permeability hypothesis of COVID-19-related microvascular damage and acral capillary dysfunction with leakage resulting in puffy hands.	Ciaffi et al., 2021 [8]
Raynaud’s disease and phenomenon	Painful, red-purple to blue discoloration with swelling--that predominantly affects the distal fingers of the hands--occurs.	Ravaglia et al., 2011 [1], Bickel et al., 2017 [9]
RS3PE	This condition occurs in elderly individuals (over 50 years of age) with the sudden onset of seronegative symmetric polyarthritis and bilateral hand swelling (caused by pitting edema), with or without tenderness. The feet are also usually affected, and the rheumatoid factor is negative. Individuals have a positive fist sign; finger flexion is limited. The clinical features respond dramatically and rapidly to treatment with systemic corticosteroids.	Joshi et al., 2009 [10]
Thoracic outlet syndrome	There are several etiologies for thoracic outlet syndrome; a cervical rib is the most common. Venous thoracic outlet syndrome can result from effort-induced (such as strenuous and repetitive exercise of the upper extremities) thrombosis of the axillary and subclavian veins associated with compression of the subclavian vein between the clavicle and the first rib. Neurologic and vascular symptoms result from the compression of the subclavian artery or vein or both and/or the brachial plexus lower roots. In addition to the neurologic and vascular manifestations, pain, erythema or bluish discoloration, and hand swelling may also be observed. Management includes either conservative measures (such as analgesics and physical therapy), or a muscle block (using either a local anesthetic or botulinum toxin), or decompression surgery.	Ravaglia et al., 2011 [1], Studdiford and Stonehouse, 2009 [3], Kalchiem-Dekel et al., 2015 [11]